Ditridecyl phthalate

ジトリデシルフタラート

[CAS No. 119-06-2]

Phthalic acid ditridecyl ester

フタル酸ジトリデシルエステル

Molecular formula: C34H58O4　　　　　Molecular weight: 530.83

ABSTRACT

Ditridecyl phthalate was studied for oral toxicity in rats in a single dose toxicity test at doses of 0 and 2000 mg/kg. An LD50 value of more than 2000 mg/kg was found for both sexes.

Ditridecyl phthalate was studied for oral toxicity in rats in an OECD combined repeat dose and reproductive/developmental toxicity screening test at doses of 0, 10, 50 and 250 mg/kg/day.

With regard to repeat dose toxicity, no deaths were observed in any animals. Increased salivation was observed in males of the 50 and 250 mg/kg/day groups. Suppression of body weight gain was observed in females of the 50 and 250 mg/kg/day groups. An increase in liver weight was noted in males of the 250 mg/kg/day group and in females of the 50 and 250 mg/kg/day groups. Hypertrophy of centrilobular hepatocytes was observed in males and females of the 50 and 250 mg/kg/day groups. An increase in kidney weight was found in males of the 250 mg/kg/day group. ALP activity increased after treatment of this compound at 250 mg/kg/day. The NOEL for repeat dose toxicity is considered to be 10 mg/kg/day in males and females.

Regarding reproductive/developmental toxicity, no adverse effects were observed on copulation, fertility, and delivery in any groups. Poor lactation was observed in the 250 mg/kg/day group. Viability of pups was slightly decreased in this group. However, there were no adverse effects of the compound on sex ratio, body weight changes, and morphological appearance of pups. The NOELs for reproductive/developmetal are considered to be 250 mg/kg/day in males, 50 mg/kg/day in females, and 250 mg/kg/day in pups, respectively.

Ditridecyl phthalate was not mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA, with or without an exogenous metabolic activation system.

Ditridecyl phthalate did not induce structural chromosomal aberrations and polyploidy in CHL cells, with or without an exogenous metabolic activation system.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Oral Toxicity１）

Purity	:	93.7-100.0 %(Converted by ester value, 198-212)
Test species/strain	:	Rat/Crj:CD(Sprague-Dawley)
Test method	:	OECD Acute Oral Toxicity Test
Route	:	Oral(Gavage)
Doses	:	0(vehicle), 2000 mg/kg
Number of animals/group	:	Males, 5; females, 5
Vehicle	:	Corn oil
GLP	:	Yes

　Test results:

No death occurred of either males or females in the treated groups. No effects were found on general condition, body weight changes or autopsy findings.

LD50: Male, > 2000 mg/kg; female, > 2000 mg/kg

2. Repeat Dose and Reproductive/Developmental Toxicity１）

Purity	:	93.7-100 %(converted by ester value, 198-212)
Test species/strain	:	Rat/Crj:CD(Sprague-Dawley)
Test method	:	OECD Combined Repeat Dose and Reproductive/ Developmental Toxicity Screening Test
Route	:	Oral(Gavage)
Doses	:	0(vehicle), 10, 50, 250 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	:	Male, day 43 Females, day 4 of lactation
GLP	:	Yes

　Test results

<Repeat dose toxicity>

No deaths were observed. Increased salivation was transiently observed in male animals of the 50 and 250 mg/kg groups after the day 10 of treatment until the autopsy. No adverse effects were detected on food consumption in males and females of any group, whereas suppression of body weight gain was observed in females of the 50 and 250 mg/kg groups. No adverse effects of ditridecyl phthalate were found on the general condition in females and on body weight gain in males.

Increase in liver weight was observed in males of the 250 mg/kg group and in females of the 50 and 250 mg/kg groups. On histopathological examination of liver, hypertrophy of the centrilobular hepatocytes was observed in males and females of the 50 and 250 mg/kg groups, and catalase positive granules in centrilobular hepatocytes were increased in males, as well. An increase in kidney weight was found in males of the 250 mg/kg group. On histopathological examination, eosinophilic bodies in renal tubular cells were increased in males of the 250 mg/kg group. In addition, basophilic tubules in the cortex which appeared to be regeneration foci resulting from necrosis of renal tubular epithelium were observed in this group. Hyperplasia of the pelvic epithelium and transitional cells of the urinary bladder was found in females of the 250 mg/kg group, while ditridecyl phthalate did not affect kidney weight in females. On urinary testing and hematological examination, no adverse effects of ditridecyl phthalate were noted. On blood chemical examination in males, ALP activity was found to be increased after the treatment of ditridecyl phthalate at 250 mg/kg.

No testicular toxicity was detected in any groups.

The no observed effect dose level(NOEL) for repeat dose toxicity is considered to be 10 mg/kg/day in males and females.

< Reproductive and developmental toxicity>

No adverse effects were observed on copulation, fertility, maintenance of pregnancy, and delivery in any groups. Poor lactation was observed in the 250 mg/kg group. Viability of neonates was slightly decreased in the 250 mg/kg group. However, there were no adverse effects of ditridecyl phthalate on sex ratio, body weight changes, and morphological appearance of pups.

NOELs for reproductive and developmental toxicity are considered to be 250 mg/kg/day in males, 50 mg/kg/day in females, and 250 mg/kg/day in pups, respectively.

3. Genetic Toxicity

3-1. Bacterial test２）

Purity	:	99.82 %
Test species/strains	:	S. typhimurium TA100, TA1535, TA98, TA1537, E. coli WP2 uvrA
Test method	:	Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)and OECD Guidelines No. 471 and 472
Procedures	:	Pre-incubation method
Solvent	:	DMSO
Positive controls	:	-S9 mix; 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide(TA100, TA98 and WP2 uvrA), Sodium azide(TA1535), 9-Aminoacridine hydrochloride(TA1537) +S9 mix; 2-Aminoanthracene(all strains)
Doses	:	-S9 mix; 156, 313, 625, 1250, 2500 and 5000 μg/plate +S9 mix; 156, 313, 625, 1250, 2500 and 5000 μg/plate
S9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	3
Number of replicates	:	2
GLP	:	Yes

　Test results:

This chemical did not induce gene mutations in the S. typhimurium and E. coli strains. No toxicity was observed up to a concentration of 5000 μg/plate, with or without metabolic activation.

Genetic effects:
S. typhimurium TA100, TA1535, TA98 and TA1537

	+	?	-
Without metabolic activation:	[ ]	[ ]	[*]
With metabolic activation:	[ ]	[ ]	[*]

E. coli WP2 uvrA

	+	?	-
Without metabolic activation:	[ ]	[ ]	[*]
With metabolic activation:	[ ]	[ ]	[*]

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

Purity	:	99.82 %
Type of cell used	:	Chinese hamster lung(CHL)cells
Test method	:	Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)and OECD Guideline No. 473
Solvent	:	DMSO
Positive controls	:	-S9 mix, Mitomycin C +S9 mix, Cyclophosphamide
Doses	:	-S9 mix(continuous exposure): 0, 1188, 2375, 4750 μg/mL -S9 mix(short-term exposure): 0, 1188, 2375, 4750 μg/mL +S9 mix(short-term exposure): 0, 1188, 2375, 4750 μg/mL
S9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	2
GLP	:	Yes

　Test results:

This chemical did not induce structural chromosomal aberrations in the absence or presence of an exogenous metabolic activation system.

Genetic effects:

	clastogenicity			polyploidy
	+	?	-	+	?	-
Without metabolic activation:	[ ]	[ ]	[*]	[ ]	[ ]	[*]
With metabolic activation:	[ ]	[ ]	[*]	[ ]	[ ]	[*]