Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
other information
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: secondary literature - cited from OECD SIDS and US EPA

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report date:
2006

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
Principles of method if other than guideline:
In a combined, repeated-dose reproductive/developmental toxicity study, Sprague-Dawley rats (10/sex/dose) were administered the test substance orally in the diet at 1000, 2750 or 7500 ppm (ca. 50, 138 or 375 mg/kg bw/day). Treatment began 2 weeks prior to mating and continued throughout maturation, mating, gestation and up today 5 of lactation (ca. 47 days). The dose levels were reduced to 900, 2500 or 6750 ppm (ca. 45, 125 or 338 mg/kg bw/d) on day 29. On study day 33, the high dose group was further reduced to 5500 ppm (ca. 275 mg/kg bw/d) due to observed toxicity. A control group of similar size was given untreated diet only.
Following 2 weeks of dosing, male and female rats were paired within their dose groups to produce litters. At day 5 post partum, all surviving females and offspring together with all adult males were killed and examined macroscopically
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
1,3-dihydro-4(or 5)-methyl-2H-benzimidazole-2-thione, zinc salt
EC Number:
262-872-0
EC Name:
1,3-dihydro-4(or 5)-methyl-2H-benzimidazole-2-thione, zinc salt
Cas Number:
61617-00-3
Molecular formula:
C8H8N2S.1/2Zn
IUPAC Name:
Zinc bis[4(or 5)-methyl-2-thioxo-2,3-dihydrobenzimidazol-1-ide]
Details on test material:
methyl-2-mercaptobenzimidazole, zinc salt

Test animals

Species:
rat
Strain:
Sprague-Dawley

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: diet
Details on mating procedure:
Following 2 weeks of dosing, male and female rats were paired within their dose groups to produce litters
Duration of treatment / exposure:
ca. 47 days
Frequency of treatment:
daily
Duration of test:
ca. 47 days
No. of animals per sex per dose:
10/sex/dose
Control animals:
yes, concurrent vehicle

Results and discussion

Results (fetuses)

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

No significant clinical or macroscopic findings were noted; however the high incidence of mortality in the dams (9) and the limited number of viable offspring in the mid - and high-dose groups precluded meaningful evaluation, therefore effect levels for developmental toxicity could not be established.

Applicant's summary and conclusion

Conclusions:
Due to the high incidence of mortality in the dams and the limited number of viable offspring in the mid and high dose groups the results of the study are not qualified for assessment
Executive summary:

In a combined, repeated-dose reproductive/developmental toxicity study, Sprague-Dawley rats (10/sex/dose) were administered the test substance orally in the diet at 1000, 2750 or 7500 ppm (ca. 50, 138 or 375 mg/kg bw/day). Treatment began 2 weeks prior to mating and continued throughout maturation, mating, gestation and up today 5 of lactation (ca. 47 days). The dose levels were reduced to 900, 2500 or 6750 ppm (ca. 45, 125 or 338 mg/kg bw/d) on day 29. On study day 33, the high dose group was further reduced to 5500 ppm (ca. 275 mg/kg bw/d) due to observed toxicity. A control group of similar size was given untreated diet only.

Following 2 weeks of dosing, male and female rats were paired within their dose groups to produce litters. At day 5 post partum, all surviving females and offspring together with all adult males were killed and examined macroscopically.

No significant clinical or macroscopic findings were noted; however the high incidence of mortality in the dams (9) and the limited number of viable offspring in the mid - and high-dose groups precluded meaningful evaluation, therefore effect levels for developmental toxicity could not be established.