Octane-1-thiol

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:

key study

Study period:

1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study was classified as reliable with restrictions because there is a GLP and a detailed study report was provided.    

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

yes

Remarks:

concentrations were administered by inhalation instead of orally; limited information on animal husbandry and methods

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dodecane-1-thiol (CAS # 112-55-0)

IUPAC Name:

Dodecane-1-thiol (CAS # 112-55-0)

Test animals

Species:

rat

Strain:

other: Charles River COBS CD

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River
- Age at study initiation: 70 days
- Weight at study initiation:
- Fasting period before study:
- Housing: stainless steel and glass exposure chambers
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24.4°C to 28.3°C
- Humidity (%): 41% to 44%

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure (if applicable):

whole body

Details on exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: whole body stainless steel and glass exposure chamber
- Method of holding animals in test chamber: cage
- Source and rate of air: atomization chamber using an air flow rate of 100 to 150 L/minute


TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatographic method
- Samples taken from breathing zone: no

Details on analytical verification of doses or concentrations:

Measurements of the concentration within the exposure chamber was approximately 9 ppm.

Details on mating procedure:

- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1:1
- Verification of same strain and source of both sexes: yes
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy

Duration of treatment / exposure:

6 hrs/day

Frequency of treatment:

Every 24 hours

Duration of test:

Gestational days 6 though 19

Doses / concentrations

Remarks:

Doses / Concentrations:
7.4
Basis:
analytical conc.

No. of animals per sex per dose:

25 dams per dose

Control animals:

yes, concurrent no treatment

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily for mortality


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Once daily for clinical signs of toxicity


BODY WEIGHT: Yes
- Time schedule for examinations: Every three days


POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 19
- Organs examined: Abdominal and thoracic cavities and organs

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other:

Fetal examinations:

- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: one third per litter
- Skeletal examinations: Yes: two thirds per litter
- Head examinations: No data

Statistics:

All statistical analysis compared the treatment group to the control group with the level of significance at p<0.05. The male to female sex distribution and the number of litters with malformations were compared using the Chi-square test criterion with Yates' correction for two-by-two contingency tables and/or Fisher's exact probability test to judge significance in the differences. The number of early and late resorptions, nonviable fetuses and postimplantation loss were compared by the Mann-Whitney U-test to judge significance of differences. The mean number of viable fetuses, total implantations, corpora lutea and mean fetal body weights were compared by analysis of variances and the appropriate t-test (for equal or unequal variances) using Dunnett's multiple comparison tables to judge significance.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
Observations of maternal toxicity included unkept coat, matter in the vagina, ptosis of the eyelids, thinness, body weight decrease and a moribund appearance. The majority of animals also showed hair loss, reddened conjunctiva, dry matter around the nose and dry peeling skin around the ears. Adverse effects on maternal weight gain were also observed.

Effect levels (maternal animals)

1

Dose descriptor:

NOAEC

Effect level:

> 0.061 mg/L air (analytical)

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

2

Dose descriptor:

LOAEC

Effect level:

> 0.061 mg/L air (analytical)

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Necropsy, Cesarean section, and fetal morphological observations were comparable to those of the control group. no statistically significant differences in Cesarean section observations or the incidence of fetal malformations were noted.

Effect levels (fetuses)

Dose descriptor:

NOAEC

Effect level:

7.4 ppm (analytical)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: There were no toxicological significances related to the test substance

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

  

Summary of Mean Body Weight in Grams of Pregnant Rats Exposed to Dodecane-1-Thiol
	Time Following Exposure (days)
	0	6	9	12	16	20
Control	230	266	269	286	310	358
Treated	237	273	267	271	294	316

Applicant's summary and conclusion

Conclusions:

In a developmental toxicity study, dodecane-1-thiol was administered to 25 female Charles River COBS CD rats/dose by whole body inhalation at dose levels of > 0.061 mg/L for 6 hrs/day from days 6 through 19 of gestation. The developmental NOAEC is 0.061 mg/L/day.

Executive summary:

In a key developmental toxicity study (OECD 414), pregnant Charles River COBS CD rats (25/dose) were exposed to dodecane-1-thiol (CAS Number 112-55-0) by whole body inhalation at dose levels of 0, 0.04, 0.28, or 0.55 mg/L for 6 hrs/day from days 6 through 19 of gestation. Animals were sacrificed on day 19 of gestation. Organs, including the ovaries and uterine content, were examined in addition to the foetuses. 

 

Survival was not affected by exposure.  Signs of maternal toxicity included unkept coat, matter in the vagina, ptosis of the eyelids, thinness, body weight decrease and a moribund appearance. The majority of animals also showed hair loss, reddened conjunctiva, dry matter around the nose and dry peeling skin around the ears. There were no biologically meaningful or statistically significant differences in the total incidence of malformation in foetuses. The NOAEC was > 0.061 mg/L air/day (analytical) based on teratogenicity.

 

This study received a Klimisch score of 2 and was classified as reliable with restrictions because there is a GLP and a detailed study report was provided.