Semicarbazide hydrochloride

Endpoint summary

Description of key information

A draft paper from 1982 and a book from 1958 have been used to cover this endpoint as no other data are available.
Different species and routes have been used, but studies are not available.

A Testing proposal should be performed on the basis of Klimisch 4 scoring of the data, different species used and possibly different routes of administration in the reported study.

All data demonstrated LD50 in the average of 100 mg/kg

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

not specified

Remarks:

Draft report

Adequacy of study:

weight of evidence

Study period:

NA

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

No other data available

Qualifier:

no guideline followed

Principles of method if other than guideline:

This document is a preliminary draft. It has not been released formally by the office of Toxic substances, Office of the Pesticides ans Toxic substances, U.S. Environmental Protection Agency, and should not at thsi stage be construed to represent Agency policy. It is being circulated for comments on its technical merit and policy implications.

GLP compliance:

no

Test type:

other: A superficial review of available data on acute toxicity

Limit test:

no

Specific details on test material used for the study:

NA

Species:

other: Mouse, Rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

NA

Route of administration:

other: Oral, Intraperitoneal and Subcutaneous

Vehicle:

not specified

Details on oral exposure:

Not Specified

Doses:

Not Specified

No. of animals per sex per dose:

Not Specified

Control animals:

not specified

Details on study design:

Not Specified

Statistics:

Not Specified

Preliminary study:

Not Specified

Sex:

not specified

Dose descriptor:

LD50

Remarks:

Oral / Mouse

Effect level:

>= 176 mg/kg bw

Based on:

not specified

Remarks on result:

other: NA

Sex:

not specified

Dose descriptor:

LDLo

Remarks:

Oral / Rat

Effect level:

>= 10 mg/kg bw

Based on:

not specified

Remarks on result:

other: NA

Sex:

not specified

Dose descriptor:

LD50

Remarks:

Intraperitoneal / Mouse

Effect level:

>= 123 mL/kg bw

Based on:

not specified

Remarks on result:

other: NA

Sex:

not specified

Dose descriptor:

LD50

Remarks:

Intraperitoneal / Rat

Effect level:

>= 140 mg/kg bw

Sex:

not specified

Dose descriptor:

LD50

Remarks:

Subcutaneous / Mouse

Effect level:

>= 105 mg/kg bw

Remarks on result:

other: NA

Sex:

not specified

Dose descriptor:

LD50

Remarks:

Subcutaneous / Rat

Effect level:

>= 173 mg/kg bw

Based on:

not specified

Remarks on result:

other: NA

Sex:

not specified

Dose descriptor:

LD50

Remarks:

Intravenous / Mouse

Effect level:

>= 126 mg/kg bw

Based on:

not specified

Remarks on result:

other: NA

Mortality:

Not Specified

Clinical signs:

other: Not Specified

Gross pathology:

Not Specified

Other findings:

Not Specified

Not Specified

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

These old data showed that SCH may be very toxic when administered acutely to rats and mice via oral, intraperitoneal, subcutaneous and intravenous routes.
All the value obtained for the LD50 are around 100mg/kg, the test item is therefore classify as Category 3 based on the GHS criteria.

Executive summary:

These old data showed that SCH may be very toxic when administered acutely to rats and mice via oral, intraperitoneal, subcutaneous and intravenous routes.

All the value obtained for the LD50 are around 100mg/kg, the test item is therefore classify as Category 3 based on the GHS criteria.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

100 mg/kg bw

Quality of whole database:

Not correct quality

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

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:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Chemring Nobel AS, 55507861
- Expiration date of the lot/batch: 28/04/2019
- Purity test date: 99,3%
Physical staate/Appearance : White solid

RADIOLABELLING INFORMATION (if applicable)
- Radiochemical purity:
- Specific activity:
- Locations of the label:
- Expiration date of radiochemical substance:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark
- Stability under test conditions:
- Solubility and stability of the test substance in the solvent/vehicle:
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test item was moistened with distilled water.
- Preliminary purification step (if any):
- Final dilution of a dissolved solid, stock liquid or gel:
- Final preparation of a solid:

FORM AS APPLIED IN THE TEST (if different from that of starting material)

TYPE OF BIOCIDE/PESTICIDE FORMULATION (if applicable)

OTHER SPECIFICS:

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS (UK), UK
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks of age
- Weight at study initiation: the weight variation did not exceed +/-20% of the mean for each sex
- Fasting period before study: no
- Housing: in suspended solid floor polypropyene cages furnished with woodflakes
- Diet : ad libitum
- Water : ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70 % relative humidity
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

distilled water

Details on dermal exposure:

TEST SITE
- Area of exposure: shorn skin of the back and the flanks
- % coverage: 10 % of the total body surface area
- Type of wrap if used:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): distilled water
- Time after start of exposure:24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Constant volume or concentration used: yes
- For solids, paste formed: yes 2000mg/kg bw

VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:

Duration of exposure:

24 hours

Doses:

2000mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations : 30 minutes, 1, 2 and 4 hours after dosing and once daily for 14 days
After removal of the dressings and subsequently once daily for 14 days the test sites were examined for evidence of primary irritation and scored according to the scale presented in the study report.
- Frequency of body weights : prior to application of the test item in Day 0 and on Days 7 and 14
- Necropsy of survivors performed: yes, gross necropsy, consisting of an external examination and opening of the abdominal and thoracic cavities
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:- Duration of observation period following administration: 14 days (or other?)
- Frequency of observations and weighing:
- Necropsy of survivors performed: yes/no
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Preliminary study:

Initially 2 animals (1 male and 1 female) were given a single, 24-hour, semi-occluded dermal application of the test item to intact skin at a dose level of 2000 =mg/kg bw.
As no mortalities were noted a further group of aimals (4 males and 4 females) has been treated in the main test.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths

Clinical signs:

other: No signs of systemic toxicity were noted during the observation period

Gross pathology:

No abnormalities were noted at necropsy

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000mg/kg bw

Executive summary:

In a acute dermal toxicity study, performed according to the GLP and the OECD Guideline 402, groups of 5 male and 5 female rats were given a single, 24 -hour, semi-occluded dermal application of DNAN to intact skin at a dose level of 2000mg/kg bw.

There were no deaths, no signs of dermal irritation, no signs of systemic toxicity, all animals showed expected gains in body weight and no abnormalities wre noted at necropsy.

The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Correct

Justification for classification or non-classification

Semicarbazide is classified regarding acute oral toxicity, Acute Oral Toxicity 3.

A draft paper from 1982 and a book from 1958 have been used to cover this endpoint as no other data are available.
Different species and routes have been used, but studies are not available.

All data demonstrated LD50 in the average of 100 mg/kg

A testing proposal should be performed on the basis of Klimisch 4 scoring of the data, different species used and possibly different routes of administration in the reported study.

And it is classified as Acute Dermal Toxicity 5, because test substance has not been tested above 2000 mg/kg and as it is very toxic by oral route, Category 5 cannot be excluded.