Registration Dossier

Administrative data

Description of key information

Oral:

LD50 > 10000 mg/kg bw (rat, males and females); BASF AG, 1967

Dermal:

LD50 > 2000 mg/kg bw (rat, male and female); BASF SE, 2008

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: post observation period 7 days, no data on strain.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
post observation period 7 days, no data on strain.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 126-218 g

no further data
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
The doses were applied as 10%, 16% or 30% preparations of the test substance in water
Doses:
800, 1000, 1600, 3200, 6400, 10000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Group-wise documentation of clinical signs was performed over the 7 day study period.
Body weight was determined before the start of the study only, as it was needed for determination of dose.
- Necropsy of survivors performed: yes
- Other examinations performed: The clinical signs and findings were reported in summary form .
Statistics:
On the basis of the observed lethality, the LD50 value was estimated or determined using a graphical evaluation of the dose response curve on probability paper .
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Mortality:
no deaths
Clinical signs:
800-1600 mg/kg bw: no symptoms
3200-10000 mg/kg bw: piloerection and tachypnoea
Body weight:
no further data
Gross pathology:
Four animals showed chronic bronchitis and bronchi ectases, all other animals without findings in the organs . Necropsy was
performed by a pathologist .

Results are given as dead animals/total number of animals at this dose

at 24 h, 48 h and 7 days after dosing:  

800 mg/kg bw: 0/10, 0/10, 0/10  

1000 mg/kg bw: 0/10, 0/10, 0/10  

1600 mg/kg bw: 0/10, 0/10, 0/10  

3200 mg/kg bw: 0/10, 0/10, 0/10  

6400 mg/kg bw: 0/10, 0/10, 0/10  

10000 mg/kg bw: 0/10, 0/10, 0/10

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
10 000 mg/kg bw

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 adverse effect observed

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:
OECD Guideline 402 (Acute Dermal Toxicity)
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: Charles River Wiga GmbH
- Age at study initiation: male animals approx. 8 - 9 weeks, female animals approx. 12 - 13 weeks
- Weight at study initiation: males: 232-255 g; females: 206-224 g
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-26 °C
- Humidity (%): 20-80 %
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
CMC (carboxymethyl cellulose)
Details on dermal exposure:
TEST SITE
- Area of exposure: About 40 cm² (corresponds to at least 10% of the body surface)
- % coverage: at least 10 % of the body
- Type of wrap if used: semi-occlusive dressing (the bandage consists of four layers absorbent gauze, Ph. Eur. Lohmann GmbH & Co. KG
and Fixomull stretch (adhesive fleece), Beiersdorf AG)


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


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 g/kg (50% testsubstance)
- Concentration (if solution): 50 g/100 ml
- Constant volume or concentration used: yes
- For solids, paste formed: yes
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation. Recording of signs and symptoms several times on the day of application, at least once each workday for the individual animals
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,gross pathology, assessment of the skin reactions
Statistics:
not applicable
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred
Clinical signs:
No systemic clinical observations were observed during clinical examination and no local effects (skin) were observed
Body weight:
The mean body weights of the animals increased normally throughout the study period
Gross pathology:
No macroscopic pathologic findings were noted in the animals (5 males and 5 females) examined on the last day of observation
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw

Additional information

Acute toxicity: oral

There is no study available, which is performed according to the current guideline. Nevertheless the study with rats (no data on strain, only 7 days post observation) is considered of sufficient and good quality to allow the evaluation of this endpoint. The LD50 in rats (5 animals/sex/dose) was > 10 000 mg/kg bw (IBDU, purity 90 – 96 %). The only clinical symptom noted was tachypnoea and piloerection at concentrations of 3200 mg/kg bw and higher. Doses of 800, 1000, 1600, 3200, 6400 and 10000 mg/kg bw were tested (BASF AG, 1967).

 

Acute toxicity: inhalation

The results from an inhalation risk test (with outdated methodology and lack of proper analytical verification of the test  atmosphere concentration), where the rats were exposed to the dusty parts (predominant size range of 2 -20 µm) of the test substance for 8 hours at a mean nominal concentration of 2.6 mg/l indicated, that the test substance is not toxic by the inhalation route as no deaths occurred and no clinical signs were noted.

 

Acute toxicity: dermal

A GLP dermal toxicity study was conducted according to OECD guideline 402 with rats (Wistar strain, 14 days of observation). The dermal LD50 in rats (5 animals/sex) was > 2000 mg/kg bw (IBDU, purity 90.3%). There were no unusual observations of any kind at the limit dose of 2000 mg/kg bw (BASF AG, 2008).

Justification for classification or non-classification

No classification and labeling is required, as the oral LD50 was greater than 10000 mg/kg and the dermal LD50 was greater than 2000 mg/kg with no mortality observed in both studies.