Benzenepropanoic acid, 3,5-bis(1,1-dimethylethyl)-4-hydroxy-, isotridecyl ester

Toxicity to reproduction

Administrative data

Endpoint:

one-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study obtained through inquiry process; SNIF file obtained from ECHA.

Data source

Reference

Reference Type:

other: SNIF

Title:

Unnamed

Year:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]

Deviations:

not specified

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

A mixture of: esters of C14-C15 branched alcohols with 3,5-di-t-butyl-4-hydroxyphenyl propionic acid; C15 branched and linear alkyl 3,5-bis(1,1-dimethylethyl)-4-hydroxybenzenepropanoate; C13 branched and linear alkyl 3,5-bis(1,1-dimethylethyl)-4-hydroxybenzenepropanoate

EC Number:

413-750-2

EC Name:

A mixture of: esters of C14-C15 branched alcohols with 3,5-di-t-butyl-4-hydroxyphenyl propionic acid; C15 branched and linear alkyl 3,5-bis(1,1-dimethylethyl)-4-hydroxybenzenepropanoate; C13 branched and linear alkyl 3,5-bis(1,1-dimethylethyl)-4-hydroxybenzenepropanoate

IUPAC Name:

413-750-2

Constituent 2

Reference substance name:

reaction mass of: esters of C14-C15 branched alcohols with 3,5-di-t-butyl-4-hydroxyphenyl propionic acid; C15 branched and linear alkyl 3,5-bis(1,1-dimethylethyl)-4-hydroxybenzenepropanoate; C13 branched and linear alkyl 3,5-bis(1,1-dimethylethyl)-4-hydroxybenzenepropanoate

IUPAC Name:

reaction mass of: esters of C14-C15 branched alcohols with 3,5-di-t-butyl-4-hydroxyphenyl propionic acid; C15 branched and linear alkyl 3,5-bis(1,1-dimethylethyl)-4-hydroxybenzenepropanoate; C13 branched and linear alkyl 3,5-bis(1,1-dimethylethyl)-4-hydroxybenzenepropanoate

Test material form:

not specified

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

70 days

Frequency of treatment:

Dosing regime (males): 7 days/week
Dosing regime (females): 7 days/week

Details on study schedule:

Number of litters per dose/conc.: at ≥ 24 mg/kg or mg/L

No. of animals per sex per dose:

Male: 30 animals at 0 mg/kg or mg/L
Male: 30 animals at 10 mg/kg or mg/L
Male: 30 animals at 50 mg/kg or mg/L
Male: 30 animals at 1000 mg/kg or mg/L
Female: 30 animals at 0 mg/kg or mg/L
Female: 30 animals at 10 mg/kg or mg/L
Female: 30 animals at 50 mg/kg or mg/L
Female: 30 animals at 1000 mg/kg or mg/L

Results and discussion

Results: P0 (first parental generation)

Details on results (P0)

One female treated with 1000 mg/kg/day group died owing to difficult parturition (dystocia). No other compound-related deaths or clinical signs were found. No effects on the mean body weight and the mean daily food consumption of treated males were observed at any dosage, while the mean body weight of the females given 50 and 1000 mg/kg day was lower than controls, more so at 1000 mg/kg/day. The same trend was observed regarding the daily food intake. No interferences were found on the F0 reproductive performance and no effects were observed on the weight of the gonads. In fact the testis weight at 1000 mg/kg/day was higher only as absolute weight and not as percentage of the final body weight at sacrifice and no treatment related modifications were seen histologically either in testes or in epididymides of the 1000 mg/kg/day treated group.
Gestation and birth data.
The length of parturition was slightly longer at 1000 mg/day; in addition difficult parturition was found in one 1000 mg/kg/day treated female. An increase in early resorptions and a higher number of still born with a related lower number of live births was found at 1000 mg/kg/day. No other effects were seen at this and a lower doses.

Effect levels (P0)

Dose descriptor:

NOEL

Effect level:

10 mg/kg bw/day

Based on:

not specified

Sex:

male/female

Results: F1 generation

Details on results (F1)

No effects were observed on the postnatal survival development of the F1 live pups. The apparent higher frequency of female fetuses was not considered compound-related, since such an effect was not found in the females allowed to litter.

Effect levels (F1)

Dose descriptor:

NOEL

Generation:

F1

Effect level:

50 mg/kg bw/day

Based on:

not specified

Sex:

male/female

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

A lower body weight gain and mean daily food consumption was observed at 50 and 1000 mg/kg/day, more evident at 1000 mg/kg/day.

Effects on fetus (Ft generation): One malformed fetus was observed at 1000 mg/kg/day, and it was considered incidental, since it was a pluri-malformed fetus with malformations that sometimes occur in controls. No other effects were seen at this and at lower doses. The higher number of early resorptions and of still born and, the related decrease in live born observed at 1000 mg/kg/day, was interpreted as a consequence of non specific toxicity in parents (lower body weight gain and mean daily food consumption) rather than a specific effect on reproduction. No specific labelling is therefore required.

Applicant's summary and conclusion

Conclusions:

The NOEL for the F0 parents is 10 mg/kg/day and for the F1 generation progeny 50 mg/kg/day. No specific labelling is therefore required.

Executive summary:

The toxicity to reporduction of the structural analogue has been determined in a GLP study with rats according to OECD Guideline No. 415 (one-generation reproduction toxicity study;oral gavage exposure at doses of 0, 10, 50 and 1000 mg/kg bw/d). In this study the effects of the substance on the reproductive performance of male and female rats and on the subsequent development of the F1 generation were assessed

and information on possible teratogenic activity was obtained. A lower body weight gain and mean daily food consumption was observed at 50 and 1000 mg/kg/day, more evident at 1000 mg/kg/day. One malformed fetus was observed at 1000 mg/kg/day, and it was considered incidental, since it was a pluri-malformed fetus with malformations that sometimes occur in controls. No other effects were seen at this and at lower doses. The higher number of early resorptions and of still born and, the related decrease in live born observed at 1000 mg/kg/day, was interpreted as a consequence of non specific toxicity in parents ( lower body weight gain and mean daily food consumption) rather than a specific effect on reproduction. No specific labelling is therefore required. The NOEL for the F0 parents is 10 mg/kg/day and for the F1 generation progeny 50 mg/kg/day.

Since EC 700-397-7 is a near analogue to the test substance (EC 413-750-2), the experimental data from this substance were used in a read-across approach.