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Administrative data

Description of key information

- Acute oral toxicity: LD50 > 2000 mg/kg bw (Safepharm, 2000)
- Acute dermal toxicity: LD50 > 2000 mg/kg (Bioassay, 2014)

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:
supporting study
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: scientifically acceptable study report
Principles of method if other than guideline:
according to BASF-internal standard
GLP compliance:
no
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hagemann
- Weight at study initiation: 170 g
- Fasting period before study: 15-20 h
- Diet (e.g. ad libitum): Herilan MRH-Haltung; H. Eggersmann KG
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5%
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 40% (w/v)
- Amount of vehicle (if gavage): 12.5 ml/kg
Doses:
5000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
None
Clinical signs:
other: No abnormalities
Gross pathology:
Organs: nothing abnormal detected
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
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:
May 12, 2014 - June 04, 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147 as this in line with OECD 402.
GLP compliance:
yes (incl. QA statement)
Remarks:
Bioassay - Labor für biologische Analytik GmbH, Im Neuenheimer Feld 515-519, 69120 Heidelberg
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 12 weeks
- Weight at study initiation: mean body weights m: 229.6g, f: 205.6g
- Housing: Single housing in Makrolon cage, type III
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany
- Water: Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 30-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: May 19, 2014 - June 03, 2014
Type of coverage:
semiocclusive
Vehicle:
corn oil
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal and dorsolateral parts of the trunk, about 40 cm²
- % coverage: at least 10% of the body surface
- Type of wrap if used:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsing of the application site with warm water
- Time after start of exposure: 24h

VEHICLE
- Amount(s) applied (volume or weight with unit): 6.67 ml/kg bw
- Concentration (if solution): 30g/100ml
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Details on study design:
- Duration of observation period following administration: 14 days
- Mortality: A check for any dead or moribund animals was made at least once each workday.
- Frequency of observations: Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter.
- Frequency of weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Necropsy of survivors performed: yes
- Scoring of skin findings: Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), several times (see results) until the last day of observation.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred
Clinical signs:
other: No systemic clinical signs were observed during clinical examination. In all five male animals strong yellowish discoloration of the application area was noted on study day 1, which prevented evaluation of erythema. The strong discoloration decreased to s
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Conclusions:
Under the conditions of this study the median lethal dose (LD50) of the test article after dermal application was found to be greater than 2000 mg/kg bw in male and female rats.
Executive summary:

In an acute dermal toxicity study (Limit Test) according to OECD guideline 402 performed under GLP, young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the test item (as suspension in corn oil Ph.Eur.) to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days. No mortality occurred and no clinical signs were observed. Due to the strong yellowish discoloration of the application site on study day 1 no erythema could be determined. Thereafter the application area was slight yellowish discolored from study day 2 until study day 9 or 14, respectively. No erythema was noted. The mean body weight of the male animals increased within the normal range throughout the study period. The body weight of the female animals only slightly increased or stagnated during the first observation week, probably due to the bandage procedure, but increased within the normal range during the second week. Due to the fact that stagnation of body weight is commonly known for females dermally applied, this stagnation is considered to be unspecific. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study. Accordingly, the acute dermal median lethal dose (LD50) was determined to be LD50, dermal, rat > 2000 mg/kg bw.

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

Additional information

Acute oral toxicity

The acute oral toxicity of the test article was assessed according to OECD testing guideline 423 following a single oral administration to the Sprague-Dawley CD strain rat (Safepharm, 2000). A group of three fasted females was treated with the starting dose of 2000 mg/kg bw. This was followed by a group of three fasted animals of the other sex at the same dose level. The test material was administered orally as a suspension in arachis oil BP. The animals were observed 0.5, 1, 2 and 4 hours after dosing and then once daily for fourteen days. Bodyweights were recorded on Day 0 (day of dosing) and on Days 7 and 14. At the end of the observation period all animals were killed by cervical dislocation and subjected to gross necropsy. There were no deaths and no clinical signs of toxicity. All animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy. The acute oral median lethal dose, (LD50) of the test material, in the Sprague-Dawley CD strain rat, was estimated as being greater than 2500 mg/kg bodyweight. No mortalities were noted in animals treated with 2000 mg/kg bodyweight.

This result is confirmed by a supporting study predating GLP and conducted according to an internal method (BASF, 1981). In the limit test, a single dose of 5000 mg/kg bw in 0.5% CMC was applied by gavage to five male and five female Sprague-Dawley rats. No mortality occurred within the observation period of 14 days and no clinical signs were reported. Necropsy did not reveal any abnormalities. Overall, under the chosen test conditions, the test substance was not toxic after single oral administration: Oral LD50 > 5000 mg/kg bw

Acute dermal toxicity

In a GLP compliant acute dermal toxicity study following OECD guideline 402, young adult Wistar rats (5 per sex) were dermally exposed to a single dose of 2000 mg/kg bw of the test item suspended in corn oil to the clipped skin (dorsal and dorso-lateral parts of the trunk, 10% body surface) and covered by semi-occlusive dressing for 24 hours. The animals were observed for 14 days. No mortality occurred and no clinical signs were observed. Due to the strong yellowish discoloration of the application site on study day 1 no erythema could be determined. Thereafter the application area was slight yellowish discolored from study day 2 until study day 9 or 14, respectively. No erythema was noted. The mean body weight of the male animals increased within the normal range throughout the study period. The body weight of the female animals only slightly increased or stagnated during the first observation week, probably due to the bandage procedure, but increased within the normal range during the second week. Due to the fact that stagnation of body weight is commonly known for females dermally applied, this stagnation is considered to be unspecific. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study. Accordingly, the acute dermal median lethal dose was determined to be LD50, dermal, rat > 2000 mg/kg bw.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available experimental test data is reliable and suitable for the purpose of classification under Directive 67/548/EEC. Based on the data, classification for acute toxicity is not warranted under Directive 67/548/EEC.

 

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the data, classification for acute toxicity is not warranted under Regulation (EC) No.1272/2008.