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Description of key information

Oral gavage of 5000 mg/kg of the test material did not cause mortality in male and female rats. There were temporary clinical signs.
The acute dermal median lethal dose (LD50) of the analogous substance in rats with intact skin was in excess of 2000 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:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: no GLP; short report
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Remarks:
pre-dates GLP regulation
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Ltd. Margate UK
- Age at study initiation: 4 to 6 weeks
- Weight at study initiation: 70 to 90 g
- Fasting period before study: 21 h
- Housing: no data
- Diet (e.g. ad libitum): ad ibitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 2 C
- Humidity (%): ca 47%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 40 %
- Justification for choice of vehicle: Water is the vehicle of joice whenever possible.

MAXIMUM DOSE VOLUME APPLIED: 12.5 ml/kg
Doses:
0 mg/kg bw ( Control)
5000 mg/kg bw (treated)
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: twice daily
- Frequency ofweighings: days 1, 8, and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weights
Sex:
male/female
Dose descriptor:
LD0
Effect level:
5 000
Based on:
test mat.
Remarks on result:
other: No mortality occurred
Mortality:
None
Clinical signs:
Piloerection, hunched posture, and abnormal gait (waddling) occurred shortly after dosing. Piloerection was abserved also in the control group.
Body weight:
No adverse effects observed.
Gross pathology:
No abnormal findings
Other findings:
none.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral gavage of 5000 mg/kg bw of the test material did not cause mortality in male and female rats.
Executive summary:

The oral gavage of 5000 mg/kg bw of the test material did not cause mortality in male and female rats. Clinical signs were limited to temporary piloerection hunched posture and abnormal gait shortly after treatment. No adverse effects on body weights or the macroscopic appearance of organs were detected.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
Klimisch grade : 2, no GLP (predates GLP), method similar to standard method of the time

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
exposure considerations
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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: read across, GLP, acc. to Guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River UK
- Age at study initiation: 7 -8 weeks
- Weight at study initiation: 210 - 300 g
- Fasting period before study: no
- Housing: single polypropylenen cages
- Diet (e.g. ad libitum): ad lib.
- Water (e.g. ad libitum): ad lib.
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 22
- Humidity (%): 42 - 70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
occlusive
Vehicle:
water
Remarks:
suspension
Details on dermal exposure:
TEST SITE
- % coverage: ca 10
- Type of wrap if used: impermeable plaster arround the trunk

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no, but wiped with paper towel
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4mL/kg of a 500 mg/mL suspension
- Constant volume or concentration used: yes
- For solids, paste formed: yes
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observation; weekly weighing
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality observed
Mortality:
none
Clinical signs:
No abnormal observations
Body weight:
Normal development
Gross pathology:
No abnormal observations
Other findings:
None
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of Brown HH 469 in rats with intact skin was in excess of 2000 mg/kg.
Executive summary:

A study was performed te determine the acute dermal median lethal dose (LD50) of Brown HH 469 in the rat. The study was designed to meet the requirements of Annex V of the EEC Council Directive 79/831/EEC, the Organisation for Economic Co-operation and Developement (OECD), and the HSE Approved Code of Practice Notification of New Substances Regulations 1982.

A group of 10 Sprague-Dawley rats (5 males, 5 females) was given a single, 24 hour, dermal application of Brown HH 469 at a dose level of 2000 mg/kg.

No animals died during the 14 day observation period. The acute dermal median lethal dose (LD50) of Brown HH 469 was in excess of 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Klimisch grade : 2, no GLP (predates GLP), method similar to standard method of the time

Additional information

Neither oral nor dermal application of the test item to rats at the highest recommended doses caused mortality. Slight, temporary clinical signs were observed only after oral gavage.


Justification for selection of acute toxicity – oral endpoint
target substance tested

Justification for selection of acute toxicity – dermal endpoint
sole study

Justification for classification or non-classification

Not classified. There is no need for classification for acute toxicity because mortality, the relevant criterion, was not observed.