Registration Dossier

Administrative data

Description of key information

The test item did not induce toxic effects in the rat following oral or dermal administration of a single dose at a level 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
Study period:
15 February 1995 to 01 March 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to recent EU test guidance in compliance with GLP.
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winklemann, Borchen, Germany
- Age at study initiation: Males 6 -7 weeks, Females 8 - 9 weeks
- Weight at study initiation: Initial mean weight: Males 180g, Females 161g
- Fasting period before study: 16 hours prior
- Housing: Conventational conditions - Makrolon Typo-III cages, 5 to a cage
- Diet (e.g. ad libitum): Altromin 1324 pellets, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 55
- Air changes (per hr): 10 - 15 per hour
- Photoperiod (hrs dark / hrs light): 12 hour light/dark (artifical light from 6am to 6pm)
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Demineralised
Details on oral exposure:
As above; the substance was administered as a single dose of 2000 mg/kg in demineralised water.
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
Males 5
Females 5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Several times on day of administration, twice daily during the observation period (once on weekends & bank holidays)
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No animal died during the 14-day observation period.
Clinical signs:
Blue discoloration of the feces in correspondence with the color of the dye was observed after single administration of 2000 mg/kg from four hours until the 3rd day following treatment. No other signs of intoxication occurred. All animals were free of signs from the 4th day.
Body weight:
Growth of male and female rats was not affected
Gross pathology:
None of the animals sacrificed at the end of the 14-day observation period showed any noticeable gross pathological findings.
Other findings:
None
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the present investigations, the test substance is therefore to be regarded as relatively non-toxic.

LD50 > 2000 mg/kg body weight.
Executive summary:

Study conducted to recent EU & OECD test guidance in compliance with GLP.

Based on the present investigations, the test substance is regarded as relatively non-toxic and is not classified.

LD50 > 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 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:
15 February 1995 to 01 March 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to recent EU and OECD test guidance in compliance with GLP.
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winklemann GmbH
- Age at study initiation: Males 8 - 10 weeks, Females 12 - 14 weeks
- Weight at study initiation: Inital mean weight: Males - 224g, Females - 199g
- Fasting period before study: No data
- Housing: Conventional conditions, Makrolon Type-II cages, invidually
- Diet (e.g. ad libitum): Altronim 1324 pellets, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 55
- Air changes (per hr): 10 - 15 per hours
- Photoperiod (hrs dark / hrs light): 12 hours light/dark (artifical light from 6am to 6 pm)

Type of coverage:
occlusive
Vehicle:
castor oil
Remarks:
polyethoxylated (Cremophor EL)
Details on dermal exposure:
TEST SITE
- Area of exposure: Back & flanks
- % coverage: 10
- Type of wrap if used: non-irritant skin plaster (Fermoflexband)

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): No data
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
Males - 5
Females - 5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations: Several times on the day of application then twice daily (once at weekends & bank holidays). Weighing: Directly before administration, after one week and at the end of the 14 day observation period.
- Necropsy of survivors performed: yes
Statistics:
Taking into consideration available data, the dosages are selected in such a way that graded lethality rates are obtained, which allow calculation or at least an estimate of the LD50.

Sufficient characterisation of acute dermal toxicity is reached as a rule, even if no substance-related lethality occurs at a dosage of 2000 mg/kg body weight.

The dosages are given in mg/kg body weight.

The following dosage was administered:

2000 mg/kg body weight

The calculation of the amount of test substance to be administrated was done taking into account a content of 65%.

Calculation of the Median Lethal Dose (LD50)

If calculation of the median lethal dose (LD50) is possible, it is done according to Spearman-Karher. The algorithm was adopted from SACHS, L. (Angewandte Statistik, 6.Auf1. 1984 , 178).

Should there be value pairs with a mortality of 0% and 100%, the geometric mean of the corresponding dosages is regarded as the "approximate LD50 value".

If only one dose group is used, the LD50 is estimated.
Preliminary study:
Not applicable.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No animal died during the 14-day observation period.
Clinical signs:
No signs of systemic poisoning were observed after single application of 2000 mg/kg body weight.

After the 21-hour exposure the skin in the area of the application site showed a blue discoloration in all rats. This coloration persisted until the 9th day of observation. All animals were free of signs from the 10th day.
Body weight:
Growth of male and female rats was not affected.
Gross pathology:
None of the animals sacrificed at the end of the 14-day observation period showed any noticeable gross pathological findings.
Other findings:
None
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the present investigations, the test substance is therefore to be regarded as relatively non-toxic after acute dermal exposure.

LD50 > 2000 mg/kg body weight
Executive summary:

Study conducted to recent EU test guidance 92/69/EEC part B3 and OECD test guideline 402 in compliance with GLP.

Based on the study the test substance is to be regarded as relatively non-toxic after acute dermal exposure. The test substance is not classified.

LD50 > 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Testing on the above endpoints gave the following results:

 Acute toxicity: Oral.

-         LD50: >2000 mg/kg

Acute toxicity: Dermal.

-         LD50: >2000 mg/kg

Acute toxicity: Inhalation.

Not measured.

The test substance has a presumed very low vapour pressure and is a granular product, hence the potential for the generation of inhalable forms is low. In addition, production and use is done in a closed process without isolation of reaction products. The isolated product are dust free granules (non-dusty solid) which may be formulated into a liquid preparation of low volatility and the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur. Dermal exposure is considered to be the appropriate route of exposure and has been assessed accordingly. No acute inhalation test was performed.

The following information is taken into account for any hazard / risk assessment:

Oral, inhalation and dermal acute toxicity are all considered.

Value used for CSA:

LD50 (oral): 2000 mg/kg bw

LD50 (dermal): 2000 mg/kg bw

Justification for classification or non-classification

The above studies have all been ranked reliability 1 according to the Klimish et al system. This ranking was deemed appropriate because the studies were conducted to GLP and in compliance with agreed protocols. ufficient dose ranges and numbers are detailed; hence it is appropriate for use based on reliability and animal welfare grounds.

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008). No classification for acute effects is therefore required.