Dipentylammonium dipentyldithiocarbamate

Endpoint summary

Description of key information

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg body weight (Globally Harmonized Classification System-Category 4).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 March 2018 - 5 September 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

Annex 2B

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147, 24 November 2000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

Purity: >99% (nominal); a substance of Unknown or Variable composition, Complex reaction products or Biological materials (UVCB)
Description: Yellow liquid

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: Wistar (RccHan™:WIST)
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: The body weight variation did not exceed ±20% of the mean body weight at the start of treatment.
- Fasting period before study: Overnight fasting immediately before dosing and for approximately 3 to 4 hours after dosing.
- Housing: Animals assigned to the study were group housed by dose level. The animals were housed in groups of up to four in suspended solid floor polypropylene cages with stainless steel mesh lids and furnished with softwood flake bedding.
- Diet and water: With the exception of an overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing, free access to tap drinking water and food was allowed throughout the study.
- Acclimation period: At least 5 days
- Other: The animals were provided with environmental enrichment items which were analyzed and considered not to contain any contaminant at a level that might have affected the purpose or integrity of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): At least fifteen changes
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours darkness.

Route of administration:

oral: gavage

Vehicle:

arachis oil

Doses:

300 mg/kg

No. of animals per sex per dose:

1 animal per dose, followed by four animals per dose.

Control animals:

no

Details on study design:

In the absence of data regarding the toxicity of the test item, 300 mg/kg was chosen as the starting dose. In the absence of mortality at a dose level of 300 mg/kg, an additional animal was treated at 2000 mg/kg. Due to mortality at a dose level of 2000 mg/kg, an additional group of animals was treated 300 mg/kg.

A total of five animals were therefore treated at a dose level of 300 mg/kg in the study.

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose group to confirm the survival of the previously dosed animals.

Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for up to 14 days. Morbidity and mortality checks were made twice daily, early and late during normal working days, and once daily at weekends and public holidays.

Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14 or at death.

At the end of the observation period the surviving animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

At 2000 mg/kg an animal was found dead one day after dosing.

There were no deaths at 300 mg/kg.

Clinical signs:

other: At 2000 mg/kg the signs of systemic toxicity noted during the day of dosing were hunched posture and ataxia. At 300 mg/kg there were signs of systemic toxicity noted in two animals up to 3 days after dosing were pilo-erection and/or hunched posture. Thre

Gross pathology:

Abnormalities noted at necropsy of the animal treated at a dose level of 2000 mg/kg that was found dead one day after dosing were dark liver and dark kidneys.

No abnormalities were noted at necropsy of animals treated at a dose level of 300 mg/kg.

Individual Body Weights and Body Weight Changes -2000mg/kg

Dose Level (mg/kg)	Animal Number and Sex	Body Weight (g) at Day			Body Weight (g) at Death	Body Weight Gain (g) During Week
		0	7	14		1	2
2000	2-0 Female	156	-	-	143	-	-

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg body weight (Globally Harmonized Classification System-Category 4).

Executive summary:

An acute oral toxicity study was carried out in the female Wistar rat. The study was performed to the standardized guidelines, including OECD 420, EU Method B.1 and EPA OPPTS 870.1100, under GLP conditions.

Following a sighting test at dose levels of 300 mg/kg and 2000 mg/kg body weight, a further group of four fasted females was given a single oral dose of test item, as asolutioninarachis oil BP, at a dose level of 300 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

The animal treated at a dose level of 2000 mg/kg was found dead one day after dosing. All animals dosed at 300 mg/kg survived to the scheduled sacrifices.

Signs of systemic toxicity noted in the animal treated at a dose level of 2000 mg/kgthat was found dead one day after dosing were hunched posture and ataxia.

Signs of systemic toxicity noted in two animals treated at a dose level of 300 mg/kg were pilo-erection and/or hunched posture. Three animals treated at a dose level of 300 mg/kg appeared normal throughout the observation period. 

Surviving animals showed expected gains in body weight.

Abnormalities noted at necropsy of the animal treated at a dose level of 2000 mg/kgthat was found dead one day after dosing were dark liver and dark kidneys.

No abnormalities were noted at necropsy of animals treated at a dose level of 300 mg/kg.

The acute oral median lethal dose (LD₅₀) of the test item in the female Wistar strain rat was estimated to be in the range of 300 ‑ 2000 mg/kg body weight (Globally Harmonized Classification System-Category 4).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available