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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian germ cell study: cytogenicity / chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 478 (Genetic Toxicology: Rodent Dominant Lethal Test)
Version / remarks:
FDRL Proposol No. 79062-B, further defined in FDRL Protocol 6477
GLP compliance:
yes
Type of assay:
rodent dominant lethal assay

Test material

Constituent 1
Chemical structure
Reference substance name:
4-[(morpholinothio)thioxomethyl]morpholine
EC Number:
237-335-9
EC Name:
4-[(morpholinothio)thioxomethyl]morpholine
Cas Number:
13752-51-7
Molecular formula:
C9H16N2O2S2
IUPAC Name:
morpholin-4-yl morpholine-4-carbodithioate
Constituent 2
Reference substance name:
Cure-Rite® 18; commercial
IUPAC Name:
Cure-Rite® 18; commercial

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Blue Spruce Farms Inc.
- Age at study initiation: not stated.
- Weight at study initiation: 307 - 329 grams mean weight at week 1.
- Assigned to test groups randomly: yes
- Fasting period before study: no
- Housing: 1 male per wire mesh cage, 2 females per cage.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 10 days


IN-LIFE DATES: From: 31 March 1980 To: 18 June 1980

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
Corn Oil.
Details on exposure:
All housed male rats were gavaged at the appropriate dose for 56 consecutive days.
Positive control animals were dosed with Triethylenemelamine via intraperitoneal injection on the last day of the treatment period.
Duration of treatment / exposure:
Male rats were dosed for 56 consecutive days before being housed with the female rats.
Frequency of treatment:
Daily
Post exposure period:
One week for males housed with two females to allow for mating. Then the two females were replaced by two more females for one week.
Thirteen days after the midpoint of each cohabitation, all females were sacrificed and subjected to uterine examination.
After the final mating period, three males per treatment group were randomly selected for necropsy.
Doses / concentrations
Remarks:
Doses / Concentrations:

Basis:
nominal conc.
0, 6.25, 12.5 and 25 mg/kg/day. TEM 0.25 mg/Kg/day
No. of animals per sex per dose:
10 males per group, in 5 groups (labelled A, B, C, D, E).
Control animals:
yes, concurrent vehicle
Positive control(s):
triethylenemelamine
- Justification for choice of positive control(s):
- Route of administration: intraperitoneal injection on last day of treatment.
- Doses / concentrations: 0.25 m/Kg/Day.

Examinations

Tissues and cell types examined:
Male rats: The following tissues were preserved - adrenals, brain, kidneys, liver, spleen, lung/main bronchi, sciatic nerve/skeletal muscle, testes, seminal vesicles, epididymides, prostate, pancreas, spinal cord, stomach, altered tissues.
Details of tissue and slide preparation:
All tissues taken from males rats were weighed except for the sciatic nerve/skeletal muscle, pancreas and spinal cord. Organ/body weight ratios were calculated for each.
Evaluation criteria:
Female rats: uterine examination to evaluate percent pregnancy, implantation per pregnancy, pre-implantation losses, early fetal deaths per pregnancy, late fetal deaths per pregnancy, and percent early fetal deaths per dam.
Statistics:
The effects of mating and treatment and their interaction were analyzed statistically at a 0.05 level of significance. Percentages and proportions were
analyzed using 95% confidence intervals or by computation of exact probabilities. Continuous data were analyzed using a one-way completely random classification analysis of variance for fixed effects. When differences were indicated, the least significant differences test was then employed
to determine which group(s) differed from the control.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
Number of implantation sites in females from the test groups were comparable to the control group. The positive control mated females had a significantly lower number of implantation sites per females.

The mean percent of pre-implantation losses were similar to the control groups and fall within accepted limits as presented by FDRL. The positive control was significantly higher.

Mean number of early fetal deaths per pregnancy and the mean percent of early fetal deaths were comparable to the control groups. The positive control was significantly higher.

Any other information on results incl. tables

Pregnancy rates overall range: 75 - 95%

Control group (corn oil) -  85%

TEM positive control      -  90%

6.25 mg/Kg Curerite 18 - 85%

12.5 mg/Kg Curerite 18 - 95%

25.9 mg/Kg Curerite 18 - 95%

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
The data was judged to indicate that Cure-rite 18 failed to produced dominant lethal mutations.
Executive summary:

The present dose levels of Curerite 18 were able to produce a dose related decrease in body weight gains over the 56 day dosing period. It also showed that Curerite 18 did not alter pregnancy or early fetal deaths. The alterations in implantation and preimplantation losses were judged to be related to a decrease in fertility for this group in the first mating. This is supported by the number of implants per dam and percentage preimplantation losses per dam for the high dose group fall into the normal range of values under FDRL limits.

Therefore, Curerite 18 is considered to not produce dominant lethal mutations.