Single oral dose LD50 values of o-sec-butylphenol were between 500 and 1000 mg/kg in both sexes. Pathological lesions were observed in the stomach and lung.
An OECD combined repeat dose and reproductive/developmental toxicity screening test was performed in rats for o-sec-butylphenol. With regard to repeat dose toxicity, no animals died in any groups. Salivation after dosing, decrease in activity and incomplete eyelid opening were observed in males and females of the 300 mg/kg group. In addition, an ataxic gait was observed in females of the same group. An increase in relative liver weight was observed in males and females, and hypertrophy of the centrilobular hepatocytes in males of the 300 mg/kg group. Concentration of total cholesterol was also increased in males given 300 mg/kg. No adverse effects were detected on food consumption and body weight change in males and females of the 300 mg/kg group. In the 60 mg/kg group, decrease in locomotor activity was observed in a few males early in the administration period. The NOELs for repeat dose toxicity are considered to be 12 mg/kg/day in males and 60 mg/kg/day in females.
Regarding reproductive and developmental toxicity, no adverse effects were observed on copulation, fertility, maintenance of pregnancy, delivery, and lactation. In addition, o-sec-butylphenol did not affect the viability of neonates, sex ratio, body weight changes, and morphological appearance of pups. NOELs for reproductive and developmental toxicity are considered to be 300 mg/kg/day in males, females and pups.
o-sec-Butylphenol was not mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA, with or without an exogenous metabolic activation system.
o-sec-Butylphenol induced structural chromosomal aberrations in CHL cells, with or without an exogenous metabolic activation system.
| Purity | : | 99.15 % |
| Test species/strain | : | Rat/Crj:CD(SD) |
| Test method | : | OECD Test Guideline 401 |
| Route | : | Oral (gavege) |
| Doses | : | 0, 250, 500, 1000, 2000 mg/kg |
| Number of animals/group | : | Males, 5; females, 5 |
| Vehicle | : | Corn oil |
| GLP | : | Yes |
Test results:
The LD50 values were between 500 and 1000 mg/kg in both sexes.
| Purity | : | 99.15 % |
| Test species/strain | : | Rat/Crj:CD(IGS) |
| Test method | : | OECD Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test |
| Route | : | Oral (gavage) |
| Doses | : | 0 (vehicle), 12, 60, 300 mg/kg/day |
| Number of animals/group | : | Males, 13; females, 13 |
| Vehicle | : | Corn oil |
| Administration period | : | Males, 42 days Females, from 14 days prior to mating to day 3 of lactation |
| Terminal killing | : | Males, day 43 Females, day 4 of lactation |
| GLP | : | Yes |
Test results:
No animals died in any groups. Salivation after dosing, decrease in activity (decreased locomotor activity, adoption of a prone or lateral position, leaning) and incomplete eyelid opening were observed in males and females of the 300 mg/kg group. In addition, ataxic gait was observed in females of the same group. An increase in relative liver weight was observed in males and females of the 300 mg/kg group. On histopathological examination of the liver, hypertrophy of the centrilobular hepatocytes was observed in males of the 300 mg/kg group, whereas this change was not observed in females of the same group. The total cholesterol concentration was increased in the males of the 300 mg/kg group. No adverse effects were detected in terms of food consumption and body weight change in males and females of the 300 mg/kg group. The hematological examination of males revealed no adverse effects of o-sec-butylphenol. In the 60 mg/kg group, decrease in locomotor activity was observed in few males in the early administration period, but not in females. No adverse effects of o-sec-butylphenol at the dose level of 12 mg/kg were found.
The no observed effect dose levels (NOELs) for repeat dose toxicity are considered to be 12 mg/kg/day in males and 60 mg/kg/day in females.
<Reproductive and developmental toxicity>
No adverse effects were observed on copulation, fertility, maintenance of pregnancy, delivery, and lactation. In addition, o-sec-butylphenol did not affect the viability of neonates, sex ratio, body weight changes, and morphological appearance of pups.
The NOEL for reproductive and developmental toxicity is considered to be 300 mg/kg/day in males, females and offspring.
| Purity | : | 99.15 % |
| Test species/strain | : | Salmonella typhimurium TA100, TA1535, TA98, TA1537 Escherichia coli WP2 uvrA |
| Test method | : | Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) and OECD Test Guidelines 471 and 472 |
| Procedures | : | Pre-incubation method |
| Solvent | : | DMSO |
| Positive controls | : | -S9 mix; 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (TA100, TA98, WP2 uvrA), Sodium azide (TA1535) and Aminoacridine (TA1537) +S9 mix; 2-Aminoanthracene (all strains) |
| Doses | : | -S9 mix; 0, 12.5, 25, 50, 100, 200, 400 μg/plate +S9 mix; 0, 12.5, 25, 50, 100, 200, 400 μg/plate |
| S9 | : | Rat liver, induced with phenobarbital and 5,6-benzoflavone |
| Plates/test | : | 3 |
| Number of replicates | : | 2 |
| GLP | : | Yes |
Test results:
Genetic effects:
Salmonella typhimurium TA100, TA1535, TA98, TA1537
| + | ? | - | |
| Without metabolic activation: | [ ] | [ ] | [*] |
| With metabolic activation: | [ ] | [ ] | [*] |
Escherichia coli WP2 uvrA
| + | ? | - | |
| Without metabolic activation: | [ ] | [ ] | [*] |
| With metabolic activation: | [ ] | [ ] | [*] |
| Purity | : | 99.15 % |
| Type of cell used | : | Chinese hamster lung (CHL) cells |
| Test method | : | Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) and OECD Test Guideline 473 |
| Solvent | : | DMSO |
| Positive controls | : | -S9 mix, 1-methyl-3-nitro-1-nitrosoguanidine +S9 mix, Benzo[a]pyrene |
| Doses | : | -S9 mix (24 and 48 hr continuous treatment); 0, 40, 60, 80, 100, 120 μg/mL -S9 mix (6 hr short-term treatment); 0, 60, 80, 100, 120, 140 μg/mL +S9 mix (6 hr short-term treatment); 0, 5, 10, 20, 30, 40 μg/mL |
| S9 | : | Rat liver, induced with phenobarbital and 5,6-benzoflavone |
| Plates/test | : | 2 |
| GLP | : | Yes |
Test results:
Cytotoxicity was observed at 120 μg/mL with 24 and 48 hr continuous treatment without an S9 mix.
| Lowest concentration producing cytogenetic effects in vitro: | ||
| Without metabolic activation (48 hr continuous treatment) | : | 80 μg/mL (clastogenicity) |
| With metabolic activation (6 hr short-term treatment) | : | 20 μg/mL (clastogenicity) |
Genotoxic effects:
| clastogenicity | polyploidy | |||||
| + | ? | - | + | ? | - | |
| Without metabolic activation: | [*] | [ ] | [ ] | [ ] | [ ] | [*] |
| With metabolic activation: | [*] | [ ] | [ ] | [ ] | [ ] | [*] |
| 1) | The tests were performed by the Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano-shi, Kanagawa, 257-8523, Japan. Tel +81-463-82-4751 Fax +81-463-82-9627 |
| 2) | The test were performed by the Research Institute for Animal Science in Biochemistry and Toxicology, 3-7-11 Hashimotodai, Sagamihara-shi, Kanagawa, 229-1132, Japan. Tel +81-427-62-2775 Fax +81-427-62-7979 |