Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: WIGA, Sulzfeld
- Age at study initiation: ca. 12 weeks
- Weight at study initiation: mean male animals: 220 g, mean female animals: 180 g
- Fasting period before study: 16 hours before the study, water ad libitum
- Housing: 5 animals in V-II-A-steel-meshcages, typ DK-III
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-26 °C
- Humidity (%): 45-75%
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE (0.5% aqueous carboxymethyl cellulose)
- Concentration in vehicle: 50%
- Amount of vehicle (if gavage): 10 ml/kg bw
- Justification for choice of vehicle: Aqueous formulation corresponds to the physiological medium

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighing was performed on day 0, day 2-4, day 7 and day 13, clinicals signs were checked after
application during the first 15 minutes, at 15 and 30 minutes, after 1, 2, 4 and 5 hours, then twice on working days and once a day on weekends
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
one male animal died on day 2 and one female animal died on day 1, total 2/10 animals died
Clinical signs:
dyspnoe, apathy, staggering, scrubby fur, salivation, bad general condition
Body weight:
mean weight male animals: 220 g (days 0), 249 g (day 2-4), 280 g (day 7), 316 g (day 13)
mean weight female animals: 180 g (day 0), 198 g (day 2-4), 215 g (day 7), 227 g (day 13)
Gross pathology:
dead animals:
heart: acute dilatation of the prechambers, acute congestive hyperanemia
stomach/intestine: vascula injection, intestine: atonic
sacrificed animals:
stomach: gastroesophageal vestibule thickened, sporadic agglutination of the gastroesophageal vestibule with the peritoneum.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study the median lethal dose of the test item after oral aclministration was found to be greater than 5,000 mg/kg body weight in rats.
Executive summary:

The study was performed to assess the acute toxicity following oral administration in Wistar rats in a study performed similar to OECD 401 guideline (GLP not specified).

Single doses of 5,000 mg/kg body weight of the test material preparations in aqueous carboxymethyl cellulose (5%) were given to 5 male and 5 female fasted rats by gavage. One day after substance administration, 1 male and 1 female rat died. The dead animals showed gross pathology findings at the heart (acute dilatation of the prechambers, acute congestive hyperanemia), stomach (vascular injection) and intestine (atonic). In animals surviving the observation period of 14 days gross pathology findings at the stomach were investigated and included gastroesophageal vestibule thickened, sporadic agglutination of the gastroesophageal vestibule with the peritoneum. Clinical signs observed throughout the study were dyspnoe, apathy, staggering, scrubby fur, salivation and bad general condition. The mean body weights of the administration groups increased throughout the study period.

Under the conditions of this study, the median lethal dose of the test item after oral administration was found to be greater than 5,000 mg/kg body weight in rats.

Reason / purpose:
reference to same study
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
Jan. 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1981
Deviations:
yes
Remarks:
occlusive, only 8 days of observation, 72 h observation timepoint missing
GLP compliance:
not specified
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gaukler, Offenbach, Germany
- Weight at study initiation: male: 3.18 kg, female: 3.14 kg
- Housing: individually in stainless steel cages with wire mesh floor, 40 cm x 51 cm
- Diet: ca. 130 g per animal and day; Ovator Solikanin 4 MM; Muskator-Werke
- Water: ca. 250 ml per day and animal; tap water and deionized water
- Acclimation period: at least 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 26 °C
- Humidity (%): 50 - 80 %
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
clipped
Remarks:
at least 15 h before exposure
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin of the same animals
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): ca. 0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
8 days
Number of animals:
2 animals
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: occlusive


REMOVAL OF TEST SUBSTANCE
- Washing (if done): at the end of the exposure with lutrol and lutrol/water (1:1)
- Time after start of exposure: after 4 hours of exposure


SCORING SYSTEM: according to Draize/ as described in OECD guideline 404
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24 hours
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 48 hours
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 48 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 48 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 48 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study the substance was not irritating to the skin under the tested conditions. However, mild skin effects were observed.
Executive summary:

The present skin irritation study was performed similar to OECD guideline 404 (GLP not specified, reliability 2) with two Vienna White rabbits (f/m). The animals were treated for 4 h with the undiluted test substance under occlusive conditions and the skin reactions were observed for a period of 8 days. Mild skin effects were seen after exposure. The value for edema formation was 1 over all animals tested and 1 for individual animals. The value for erythema formation was 1.5 over all animals tested and 2 in the first animal and 1 in the second animal. In one animal, erythema formation was not fully reversible at the end of the observation period on day 8.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Principles of method if other than guideline:
BASF-Test
The inhalation hazard test demonstrates the toxicity of an atmosphere saturated with vapors of the volatile components of a test substance at the temperature chosen for vapor generation (usually 20°C). Groups of rats were sequentially exposed to the vapors, generated by bubbling 200 l/h air through a substance column of about 5 cm above a fritted disc in a glass cylinder for different time periods.
No analytical determination of the atmosphere concentrations was performed. The nominal concentration usually can be calculated as quotient of the amount of the test substance weight loss during exposure. Group-wise documentation of clinical signs was performed over the 14 day study period. Body weight of groups was determined before the start of the study and at the end of the observation period in surviving animals.
GLP compliance:
not specified
Test type:
other: Inhalation Risk Test

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Wiga, Sulzfeld, Germany
- Age at study initiation: 7-10 weeks
- Weight at study initiation: 180 - 250 g
- Housing: 3 animals per cage in Becker D III cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+- 2°C
- Humidity (%): 50+-5 %
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose/head only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
see: any other informations on materials and methods
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
7 h
Concentrations:
The dose, based on the a vapor pressure of ca. 0.000044 hPa at 20 °C, computes to ca. 0.00054 mg/l.
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were checked daily for clinical signs
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross-pathology
Statistics:
not applicable

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC0
Effect level:
0.001 mg/L air
Exp. duration:
7 h
Remarks on result:
other: All 12 animals exposed to the test material survived.
Mortality:
no deaths, all 12 animals survived the 14 days post exposure
Clinical signs:
other: wiping of the snout
Body weight:
no data
Gross pathology:
without findings

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
All 12 animals survived the inhalation risk test, where the animals were exposed to a saturated vapor of the test substance (concentration ca. 0.00045 mg/l) for 7 hours.
Executive summary:

The acute inhalation toxicity was investigated in an Inhalation Risk test with rats (reliability 2). The test was performed in principle as described in OECD test guideline 403 (GLP not specified). It demonstrates the toxicity of an atmosphere saturated with vapors of the volatile components of a test substance at 20 °C. Young adult laboratory rats, 6 per sex, were exposed sequentially to the vapors generated by bubbling 200 L/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for 7 hours. No analytical determination of the atmosphere concentrations was performed. The nominal concentration was calculated as 0.000545 mg/l based on the vapor pressure. Group-wise documentation of clinical signs was performed over a 14 day study period. All animals survided inhalative exposure and showed no gross pathology findings. Clinical symptoms soley included wiping of the snout throughout expsoure.

Based on the study findings no acute inhalation toxicity can be concluded for animals expsosed to a saturated vapor of the test item.