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EC number: 204-875-1 | CAS number: 128-03-0
Toxicological information
Toxicity to reproduction
Currently viewing:
Administrative data
- Endpoint:
- two-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
- Study period:
- 1996
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- GLP - Guideline study, tested with the source substance zinc(bis) dimethyldithiocarbamate (CAS No. 137-30-4). In accordance to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on an read-across substance
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 996
- Report date:
- 1996
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
- Deviations:
- yes
- Remarks:
- - Not all required organ weights were determined. - Sperm parameters were not assessed for all animals.
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Ziram
- EC Number:
- 205-288-3
- EC Name:
- Ziram
- Cas Number:
- 137-30-4
- IUPAC Name:
- zinc bis(dimethyldithiocarbamate)
- Reference substance name:
- zinc bis dimethyldithiocarbamate
- IUPAC Name:
- zinc bis dimethyldithiocarbamate
- Details on test material:
- - Test material: Ziram
- Lot/Batch number: V528/8331 AA
- Description: White powder
- Purity: 97.8%
- Stability: Not reported.
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Portage, Michigan, USA
- Age at study initiation: 6 weeks
- Weight at study initiation: ♂: 144-218 g, ♀: 117-174
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- other: diet
- Details on mating procedure:
- - M/F ratio: 1:1
- Length of cohabitation: Up to 15 days
- Proof of pregnancy: vaginal plug or sperm in vaginal smear referred to as day 0 of gestation
- After 10 days of unsuccessful pairing replacement of first male by another male with proven fertility.
- Further matings after two unsuccessful attempts: no
- Any other deviations from standard protocol: Litters were culled to 8 pups/litter on lactation day 4. - Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- F0 parents: from study initiation until scheduled sacrifice
F1 parents: from weaning (day 22) until scheduled sacrifice
F2 pups: from weaning (day 22) until scheduled sacrifice
Duration of exposure before mating (F0 / F1 parents): 10 weeks - Frequency of treatment:
- Ad libitum
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 60*, 180#, 540 ppm (Concentration was increased to 72 ppm (*)/ 207 ppm (#) to compensate losses during storage)
Basis:
nominal in diet
- No. of animals per sex per dose:
- 30
- Control animals:
- yes, plain diet
- Details on study design:
- - Actual doses
F0 ♂:
5, 15, 37 mg/kg/day (prior to breeding)
3, 10, 25 mg/kg/day (after breeding)
F0 ♀: 6, 17, 43 mg/kg/day (prior to breeding)
5, 13, 33 mg/kg/day (gestation)
12, 33, 85 mg/kg/day (lactation)
5, 15, 37 mg/kg/day (after weaning)
F1 ♂:
6, 18, 46 mg/kg/day (prior to breeding)
3, 10, 26 mg/kg/day (after breeding)
F1 ♀:
7, 20, 51 mg/kg/day (prior to breeding)
5, 13, 32 mg/kg/day (gestation)
11, 30, 79 mg/kg/day (lactation)
5, 14, 34 mg/kg/day (after weaning) - Positive control:
- none
Examinations
- Parental animals: Observations and examinations:
- MORTALITY
- Twice daily
CLINICAL SIGNS
- Twice daily
BODY WEIGHT
- Weekly during treatment and prior to terminal sacrifice for males.
- Confirmed mated ♀ were weighed on presumed gestation Days 0, 7, 10, 14, and 20. Nursing dams were weighed on Days 1, 4, 7, 14, and 21 post partum. After weaning (day 22) once weekly until scheduled sacrifice.
FOOD CONSUMPTION
- Daily until pairing for all animals.
- Male food consumption was measured after mating again daily until scheduled sacrifice.
- Female food consumption was measured daily throughout gestation and lactation period.
- No food consumption data was obtained during the mating period. - Oestrous cyclicity (parental animals):
- - Daily during mating.
- Sperm parameters (parental animals):
- - Only performed on males which were paired, but failed to sire a litter.
- Litter observations:
- - Sex-determination, pup viability, body weight gain, clinical signs, necropsy on dead pups, behavioural testing (F2)
- Postmortem examinations (parental animals):
- ORGAN WEIGHTS
- Yes
- Organs: testes + epididymides/ovaries, brain, pituitary gland, kidneys, liver
HISTOPATHOLOGY
- All animals from control and high-dose group.
- Tissues: Cervix, coagulating gland, epididymides, kidneys, liver, ovaries, pituitary gland, prostate, seminal vesicles, testes, uterus, vagina, vas deferens, all internal gross lesions - Postmortem examinations (offspring):
- - neuropathological examination (F2)
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Other effects:
- no effects observed
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
Details on results (P0)
F0 (♂+♀):
- Mean body weights and body weight gains in the 540 ppm group males were reduced early in the treatment period. In females mean body weights and body weight gains in the 540 ppm group were generally reduced throughout gestation and lactation and after weaning.
- Food consumption in the 540 ppm group was generally reduced in males and prior to breeding, during gestation and lactation and after weaning in females.
- Mean body weights and body weight gains in the 540 ppm group males were reduced early in the treatment period. In females mean body weights and body weight gains in the 540 ppm group were generally reduced throughout gestation and lactation and after weaning.
- Food consumption in the 540 ppm group was generally reduced in males and prior to breeding, during gestation and lactation and after weaning in females.
Effect levels (P0)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 10 mg/kg bw/day
- Sex:
- female
- Basis for effect level:
- other: (post-breeding intake ) = 10.4 mg KDDC (a.s.)/kg bw/day = 20.8 mg KDDC (50%)/kg bw/day
- Remarks on result:
- other: Generation: maternal (migrated information)
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 10 mg/kg bw/day
- Sex:
- male/female
- Basis for effect level:
- other: (post-breeding intake) = 10.4 mg KDDC (a.s.)/kg bw/day = 20.8 mg KDDC (50%)/kg bw/day
- Remarks on result:
- other: Generation: neonatal (migrated information)
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 25 mg/kg bw/day
- Sex:
- male/female
- Basis for effect level:
- other: (post-breeding intake) = 26.1 mg KDDC (a.s.)/kg bw/day = 52.2 mg KDDC (50%)/kg bw/day
- Remarks on result:
- other: Generation: reproduction (migrated information)
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Sexual maturation:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
Details on results (F1)
F1 (♂+♀):
- Mean pup body weights in the 540 ppm group litters were slightly reduced during lactation. Mean body weights and body weight gains in the 540 ppm group males were reduced throughout the treatment period. In females mean body weights and body weight gains in the 540 ppm group were generally reduced throughout gestation and lactation and after weaning.
- Food consumption in the 540 ppm group was generally reduced in males and prior to breeding, during gestation and lactation and after weaning in females.
F2 (♂+♀):
- Mean pup body weights in the 540 ppm group litters were slightly reduced during lactation and throughout the remainder of the study until the postnatal day 70 neuropathology evaluation.
- Mean pup body weights in the 540 ppm group litters were slightly reduced during lactation. Mean body weights and body weight gains in the 540 ppm group males were reduced throughout the treatment period. In females mean body weights and body weight gains in the 540 ppm group were generally reduced throughout gestation and lactation and after weaning.
- Food consumption in the 540 ppm group was generally reduced in males and prior to breeding, during gestation and lactation and after weaning in females.
F2 (♂+♀):
- Mean pup body weights in the 540 ppm group litters were slightly reduced during lactation and throughout the remainder of the study until the postnatal day 70 neuropathology evaluation.
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
Table 7.8.1-A1 Body weight changes in reproductive toxicity study |
|||||||||||
Parameter |
Generation |
Controls |
60 ppm |
180 ppm |
540 ppm |
Dose-response +/– |
|||||
♂ |
♀ |
♂ |
♀ |
♂ |
♀ |
♂ |
♀ |
♂ |
♀ |
||
Body weight [g] |
|||||||||||
average weight on gestation |
F0 dams |
/ |
348.4 |
/ |
338.6 |
/ |
356.0 |
/ |
343.8 |
/ |
− |
F1 dams |
/ |
357.1 |
/ |
339.1 |
/ |
344.7 |
/ |
316.7* |
/ |
− |
|
average pup weight on lactation Day 21 |
F1 pups |
44.8 |
42.8 |
44.6 |
41.8 |
46.3 |
43.5 |
40.2* |
37.7* |
− |
− |
F2 pups |
40.7 |
39.5 |
41.0 |
39.3 |
44.1 |
41.2 |
38.5 |
36.9 |
− |
− |
|
* statistically significant different from control p </= 0.05 |
|||||||||||
Applicant's summary and conclusion
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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