Reaction mass of 2-ethylpropane-1,3-diol and 5-ethyl-1,3-dioxane-5-methanol and propylidynetrimethanol

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1994

Reference 2

Reference Type:

publication

Title:

Newsletter

Author:

JETOC (Japan Chemical Industry Ecology-Toxicology & Information Center)

Year:

1995

Bibliographic source:

JETOC Information Sheet 18, 8-11

Reference 3

Reference Type:

review article or handbook

Title:

Toxicology Profile of 1,1,1-trimethylolpropane

Author:

BIBRA (The British Industrial Biological Research Association)

Year:

1996

Bibliographic source:

Bibra Toxicology International, Information Department, Carshalton , Surrey AM54DS, UK

Reference 4

Reference Type:

publication

Title:

Consensus Report for Trimethylolpropane.Scientific Basis for Swedish Occupational Standards XVI

Author:

Criteria Group for Occupational Standards (ed. Per|Lundberg)

Year:

1995

Bibliographic source:

Arbete Och Haelsa 19, 33-35

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD 422

Principles of method if other than guideline:

The study was a combined repeat dose and reproductive/developmental toxicity screening study

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Propylidynetrimethanol

EC Number:

201-074-9

EC Name:

Propylidynetrimethanol

Cas Number:

77-99-6

Molecular formula:

C6H14O3

IUPAC Name:

2-ethyl-2-(hydroxymethyl)propane-1,3-diol

Details on test material:

Trimethylolpropane, purity 99.9%. A read across is proposed from this substance based on the structural similarity of the two substances.

Test animals

Species:

rat

Strain:

other: Slc:SD

Details on test animals or test system and environmental conditions:

The animals were male and female Slc:SD rats. At study initiation the males weighed 304-343 g, and the females 196-226 g. The rats were acclimatised for 5 days.
Pregnant females were housed individually. Food and water were provided ad libitum. The room temperature was 22-24°C, humidity 50-60%, with a 12 hour light/dark cycle.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

The test substance was dissolved in distilled water. Dosing began 2 weeks prior to mating and continued throughout the mating period. Females were dosed throughout pregnancy and up to lactation day (LD) 4. Dosing of the males continued during this period.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Details on analytical verification were not provided.

Details on mating procedure:

Rats were mated 1:1 until pregnancy occurred. Day 0 of pregnancy was defined as the day sperm was present.

Duration of treatment / exposure:

Males were exposed for 45 days, females were exposed for 14 days before mating until LD4.

Frequency of treatment:

Daily

Duration of test:

The animals were 10 weeks old at mating. Males were sacrificed on day 46. Females and their pups were sacrificed on LD 4.

No. of animals per sex per dose:

12 rats/sex/dose

Control animals:

yes, concurrent vehicle

Details on study design:

No further details on study design are available.

Examinations

Ovaries and uterine content:

The ovaries and uterine content were examined after termination, the number of corpora lutea, implantations and early resorptions were recorded.

Fetal examinations:

External foetal examinations were conducted.

Statistics:

Statistical analyses were performed but the methods were not provided.

Indices:

The following reproductive indices were calculated: copulation index, fertility index, gestation index, implantation index, delivery index, birth index and viability index.

Historical control data:

No historical control data were provided.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
There were no maternal signs of toxicity up to the highest dose tested.

Effect levels (maternal animals)

1

Key result

Dose descriptor:

NOAEL

Effect level:

800 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

2

Key result

Dose descriptor:

NOAEL

Effect level:

200 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

body weight and weight gain

Maternal abnormalities

Key result

Abnormalities:

no effects observed

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
There were no effects indicative of developmental toxicity

Effect levels (fetuses)

Key result

Dose descriptor:

NOAEL

Effect level:

800 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no effect observed

Fetal abnormalities

Key result

Abnormalities:

no effects observed

Overall developmental toxicity

Key result

Developmental effects observed:

no

Any other information on results incl. tables

The NOAEL for development toxicity was 800 mg/kg/day.

Applicant's summary and conclusion

Conclusions:

No relevant effects were seen in this study: the NOAEL for developmental toxicity was 800 mg/kg bw/d.

Executive summary:

The developmental toxicity of TMP was investigated in a screening study (OECD 422) in rats performed at dose levels of up to 800 mg/kg bw/d. Males were exposed for 45 days, females were exposed for 14 days before mating until LD4. T he ovaries and uterine content were examined after termination, the number of corpora lutea, implantations and early resorptions were recorded. External foetal examinations were conducted. No relevant effects were seen in this study: the NOAEL for developmental toxicity was 800 mg/kg bw/d.

Categories Display