Cyclohexene

シクロヘキセン


[CAS No. 110-83-8]

1,2,3,4-Tetrahydrobenzene

Molecular formula: C6H10　Molecular weight: 82.14

ABSTRACT

Cyclohexene was studied for oral toxicity in rats of both sexes in a single dose toxicity test at doses of 0, 500, 1000 and 2000 mg/kg. The single dose oral toxicity test revealed LD50 values to be between 1000 and 2000 mg/kg for both sexes.

Cyclohexene was studied for oral toxicity in rats in the OECD test guideline 422 at doses of 0, 50, 150 and 500 mg/kg/day.

In the repeated dose toxicity, salivation were observed in the 150 mg/kg or more groups in both sexes, and lacrimation in the 150 mg/kg or more groups of males and the 500 mg/kg group of females. The test substance had no effect on body weight and food consumption in any treatment group. Blood chemical examination showed increase in the total bile acids in the males receiving 150 mg/kg or more and the 50 mg/kg or more groups of females, along with decrease in triglycerides in the 500 mg/kg males. On gross and histological examination, no adverse effects of the test substance were evident. In the 500 mg/kg males, increase in the relative kidny weights were observed.

The NOEL for repeated dose toxicity is considered to be 50 mg/kg/day for males and less than 50 mg/kg/day for females.

In terms of reproductive/developmental toxicity, no adverse effects were observed in terms of the estrus cycle, copulation and fertility results or delivery parameters. No abnormal findings related to the test substance were noted on external examination, clinical signs, growth or necropsy of the offspring.

The NOELs for reproductive and developmental toxicity are considered to be 500 mg/kg/day for both parental animals and offspring.

Reverse mutation assays using microorganisms (Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA) were conducted to assess the potential of cyclohexene to induce gene mutations. No mutagenic activity was found in bacteria under the present experimental conditions.

In vitro chromosomal aberration tests using cultured mammalian cells (CHL/IU) were conducted to assess the potential of cyclohexene to induce chromosomal aberrations. Neither structural nor numerical chromosome aberrations were detected under the present experimental conditions.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Oral Toxicity 1)

Purity:98.6 wt%
Test species/strain:Rat/Crj:CD(SD)
Test method:OECD Test Guideline 401
　Route:Oral (gavage)
　Dosage:0 (vehicle), 500, 1000, 2000 mg/kg
　Number of animals/group:Males, 5; females, 5
　Vehicle:Corn oil
GLP:Yes

　Test results:

Mortalities occurred in both male and female groups given 2000 mg/kg. Hypoactivity and lacrimation were observed in both sexes. Each 3 of 5 animals of male and female rats died within 3 days after 2000 mg/kg dosing. Necropsy of these dead animals revealed pulmonary congestion. Abnormal gait, adoption of a prone position, salivation, piloerection and tremors were also observed in some animals before death.

The LD50 values were found to be between 1000 and 2000 mg/kg for both sexes.

2. Repeated Dose and Reproductive/Developmental Toxicity 1)

Purity:98.6 wt%
Test species/strains:Rat/Crj:CD(SD)IGS
Test method:OECD Test Guideline 422
　Route:Oral (gavage)
　Dosage:0 (vehicle), 50, 150, 500 mg/kg/day
　Number of animals/groupMales, 12; females, 12
　Vehicle:Corn oil
　Administration period:Males, 48 days
Females, from 14 days before mating to day 4 of lactation
　Terminal killing:Males, day 49
Females, day 5 of lactation
GLP:Yes

　Test results:

<Repeated dose toxicity>

There was no animal mortality related to the test substance treatment. Salivation was apparent in the 150 mg/kg or more groups in both sexes, and lacrimation were observed in the 150 mg/kg or more males and the 500 mg/kg females. The test substance had no effect on body weights or food consumption in any treatment group. Blood chemical examination showed increase in the total bile acids in the 150 mg/kg or more males and the 50 mg/kg or more females, and decrease in triglycerides in the 500 mg/kg males. On gross and histological examination, no adverse effects of the test substance were apparent. However, relative kidney weights were increased in the 500 mg/kg males.

The NOEL for repeated dose toxicity is considered to be 50 mg/kg/day for males and less than 50 mg/kg/day for females.

<Reproductive and developmental toxicity>

Regarding the reproductive ability of parent animals, no effects were detected on the estrus cycle, copulation index, fertility index, gestation length, numbers of corpora lutea or implantations, implantation index, gestation index, delivery index, purturition or maternal behavior. There were no significant differences in numbers of offspring or live offspring, the sex ratio, live birth index, viability index or body weights. No abnormal findings related to the test substance were noted on external examination, in clinical signs, or on necropsy of the offspring.

The NOELs for reproductive and developmental toxicity are considered to be 500 mg/kg/day for both parental animals and offspring.

3. Genetic Toxicity

3-1. Bacterial test 2)

Purity:98.63 wt%
Test species/strains:Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Chemical Substances Control Law of Japan) and OECD Test Guideline 471
　Procedures:Pre-incubation method
　Solvent:Ethanol
　Positive controls:-S9 mix; 2-(2-Furyl)-3-(5-nitro-2-furyl) acrylamide (TA100, TA98 and WP2 uvrA), Sodium azide (TA1535) and 2-Methoxy-6-chloro-9-[3-(2-chloroethyl)-aminopropylamino] acridine・2HCl (TA1537)
+S9 mix; Benzo[a]pyrene (TA100, TA98, TA1537) and 2-Aminoanthracene (TA1535 and WP2 uvrA)
　Dosage:-S9 mix; 0, 19.5, 39.1, 78.1, 156, 313, 625, 1250 mg/plate (TA100, TA1535, TA98, TA1537)
-S9 mix; 0, 78.1, 156, 313, 625, 1250, 2500, 5000 mg/plate (WP2 uvrA)
+S9 mix; 0, 19.5, 39.1, 78.1, 156, 313, 625, 1250 mg/plate (all strains)
　S9:Rat liver, induced with phenobarbital and 5, 6-benzoflavone
　Plates/test:3
GLP:Yes

　Test results:

No mutagenic activity was found in the S. typhimurium and E. coli strains. Toxicity was not observed in any strain, with or without metabolic activation.

Genetic effects:
Salmonella typhimurium TA100, TA1535, TA98, TA1537
+?-
Without metabolic activation:[ ][ ][*]
With metabolic activation:[ ][ ][*]

Genetic effects:
Escherichia coli WP2 uvrA
+?-
Without metabolic activation:[ ][ ][*]
With metabolic activation:[ ][ ][*]

3-2. Non-bacterial in vitro test (chromosomal aberration test) 2)

Purity:98.63 wt%
Type of cell used:Chinese hamster lung (CHL/IU) cells
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Chemical Substances Control Law of Japan) and OECD Test Guideline 473
　Solvent:Ethanol
　Positive controls:-S9 mix; Mitomycin C
+S9 mix; Cyclophosphamide
　Dosage:-S9 mix (short-term treatment); 0, 100, 150, 200, 250, 300, 350 and 400 μg/mL
+S9 mix (short-term treatment); 0, 100, 150, 200, 250, 300, 350 and 400 μg/mL
-S9 mix (continuous treatment 24 and 48 hrs); 0, 100, 150, 200, 250, 300, 350 and 400 μg/mL
　S9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:2
GLP:Yes

　Test results:

No increase in chromosomal aberrations was observed in the test with either the short-term treatment (-S9 and +S9) or continuous treatment.

Genotoxic effects:
clastogenicitypolyploidy
+?-+?-
Without metabolic activation:[ ][ ][*][ ][ ][*]
With metabolic activation:[ ][ ][*][ ][ ][*]

1)The tests were performed by the Biosafety Research Center, Foods, Drugs and Pesticides(An-pyo Center), 582-2 Shioshinden, Fukude-cho, Iwata-gun, Shizuoka, 437-1213, Japan. Tel +81-538-58-1266 Fax +81-538-58-1393
2)The tests were performed by the Bozo Research Center Inc., 1284 Kamado, Gotemba-shi, Shizuoka, 412-0039, Japan. Tel & Fax +81-550-82-9922