Registration Dossier

Toxicological information

Endpoint summary

Currently viewing:

Administrative data

Description of key information

In the key acute oral toxicity study (Younger Laboratories, 1967) ATMP-H was administered to Sprague-Dawley rats as aqueous solutions at doses of 2000, 2510, 3160 and 3980 mg/kg bw, by oral gavage. There were 0, 1, 2 and 5 deaths, respectively. Survival time was several hours to four days with most deaths occurring "overnight". Toxic symptoms included weakness in one to two hours with diarrhoea, salivation and tremors. At macroscopic examination inflammation of the gastrointestinal mucosa as well as renal and liver hyperaemia were observed. The LD50 for the test substance was calculated to be 2910 mg/kg bw.

In the key acute dermal toxicity study (Younger Laboratories, 1967) conducted prior to the adoption of OECD test guidelines and GLP, ATMP-H was applied to the clipped, intact skin, under an occlusive dressing, for up to 24 hours, at doses of 1000, 1580, 2510, 3980 and 6310 mg/kg bw (one New Zealand white rabbit per dose). There were no deaths, so no macroscopic examination was conducted. Activity and appetite were temporarily reduced in the two highest-dose group animals. The LD50 was >6310 mg/kg bw. 

The inhalation endpoint was waived as reliable data via the oral and dermal routes are available.

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:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
Conducted prior to the adoption of OECD test guidelines.
Deviations:
yes
Remarks:
Limited detail on test substance, and methodology.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: Males: 230 - 250 g. Females: 210 - 225 g.
- Fasting period before study: No data
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data


IN-LIFE DATES: No data
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: No data.
Doses:
2000, 2510, 3160 and 3980 mg/kg bw (as a 25 % aqueous solution).
No. of animals per sex per dose:
Two or three depending on dose (five in total/dose).
Control animals:
no
Details on study design:
- Duration of observation period following administration: No data, but at least four days.
- Frequency of observations and weighing: Not stated
- Necropsy of survivors performed: No
- Other examinations performed: clinical signs, and gross pathology.
Statistics:
LD50 calculated by a modification of the method of E.J. de Beer (no further detail, calculation not presented).
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 910 mg/kg bw
95% CL:
>= 2 530 - <= 3 345
Mortality:
No deaths at the lowest dose of 2000 mg/kg bw. There were one, two and five deaths in the 2510, 3160 and 3980 mg/kg bw groups, respectively. Survival time was several hours to four days, with most death occurring "overnight" (it is not clear if this means the night after the dosing).
Clinical signs:
Weakness in one to two hours with diarrhoea, salivation and tremors.
Body weight:
Body weights do not appear to have been measured apart from prior to dosing.
Gross pathology:
Inflammation of the gastrointestinal mucosa as well as liver and renal hyperaemia.
Other findings:
None
Interpretation of results:
GHS criteria not met
Conclusions:
In a well conducted acute oral study (reliability score 2), conducted according to a protocol similar to the now deleted OECD 401, but not to GLP, an LD50 of 2910 mg/kg bw was determined for Dequest 2000 in the rat.
Executive summary:

ATMP-H (Dequest 2000) was administered to Sprague-Dawley rats (two or three per sex depending on dose; five total) as aqueous solutions at doses of 2000, 2510, 3160 and 3980 mg/kg bw, by oral gavage. Observations were made for clinical signs and the viscera of the animals that died were examined macroscopically. There were 0, 1, 2 and 5 deaths, respectively. Survival time was several hours to four days with most deaths occurring "overnight". Toxic symptoms included weakness in one to two hours with diarrhoea, salivation and tremors. At macroscopic examination inflammation of the gastrointestinal mucosa as well as renal and liver hyperaemia were observed. The LD50 for the test substance was calculated to be 2910 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 910 mg/kg bw

Acute toxicity: via inhalation route

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
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
Conducted prior to adoption of OECD test guidelines.
Deviations:
yes
Remarks:
Limited details on methods and animal conditions.
Principles of method if other than guideline:
Method: other: Not stated. Insufficient detail to fully assess comparability with OECD guideline.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: Males: 2.3-2.5 kg. Females: 2.0 and 2.1 kg.
- Fasting period before study: No data
- Housing: Individually (cage type to stated)
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data


IN-LIFE DATES: No data
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: No data
- % coverage: No data
- Type of wrap if used: "plastic strips"


REMOVAL OF TEST SUBSTANCE
- Washing (if done): No data


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): No data
- Concentration (if solution): 25% aqueous solution
- Constant volume or concentration used: yes


VEHICLE
- Amount(s) applied (volume or weight with unit): No data
- Concentration (if solution): 25% solution
Duration of exposure:
24 hours
Doses:
1000, 1580, 2510, 3980 and 6310 mg/kg bw
No. of animals per sex per dose:
One
Control animals:
no
Details on study design:
- Duration of observation period following administration: Not clear, but at least five days.
- Frequency of observations and weighing: Body weights appear to have been measured prior to dosing and five days after dosing.
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs and gross pathology of animals that die.
Statistics:
None
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 6 310 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred at any dose.
Clinical signs:
Activity and appetite were temporarily reduced after doses of 3980 and 6310 mg/kg bw.
Body weight:
No apparent effects.
Gross pathology:
No deaths so not conducted.
Other findings:
None
Interpretation of results:
GHS criteria not met
Conclusions:
In a well conducted acute dermal study (reliability score 2), conducted according to a protocol similar to OECD 402, but not to GLP, a dermal LD50 of >6310 mg/kg bw was determined for ATMP-H (Dequest 2000) in the rabbit.
Executive summary:

In an acute dermal toxicity study conducted prior to the adoption of OECD test guidelines and GLP, Dequest 2000 was applied to the clipped, intact skin, under an occlusive dressing, for up to 24 hours, at doses of 1000, 1580, 2510, 3980 and 6310 mg/kg bw (one New Zealand white rabbit per dose). The animals were then observed for clinical signs of toxicity (no further details). There were no deaths and therefore no macroscopic examination was conducted. Activity and appetite were temporarily reduced in the two highest-dose animals. The LD50 was >6310 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
6 310 mg/kg bw

Additional information

There were two reliability score 2 studies for each of the oral and dermal routes. From these the most recently conducted study was selected as the key study. The other available studies are however supportive of the findings in the key studies.

Justification for classification or non-classification

Based on the available data, no classification is required for acute toxicity for ATMP-H according to Regulation (EC) No 1272/2008.