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Administrative data

Description of key information

The test article is virtually non-toxic after a single ingestion with an oral LD50 of greater than 7000 mg/kg body weight. The substance appears also not toxic after short-term inhalation.

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:
12 Feb - 5 Mar 1980
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 401 (Acute Oral Toxicity)
Version / remarks:
(adopted 1981)
GLP compliance:
yes
Remarks:
A statement of the Quality Assurance Unit was added.
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Tif: RAIf (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 7-8 weeks
- Weight at study initiation: males: 176-204 g; females: 180-197 g
- Fasting period before study: Fasted overnight
- Housing: 5 animals per Makrolon cage (type 3)
- Diet (ad libitum): NAFAG, Gossau SG
- Water: ad libitum
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2
- Humidity (%): 55+/-10
- Photoperiod (hrs dark / hrs light): 10 h light day
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
PEG400
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 20 mL/kg bw


DOSAGE PREPARATION:
Test substance was suspended to achieve the corresponding dosage level. Before treatment the suspension was homogeneously dispersed with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer.
Doses:
4000, 5000, 6000, 7000 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
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight (prior to treatment, day 7, day 14)
Statistics:
LD50 including 95% confidence limits are calculated by the logit model.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 7 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality occurred.
Mortality:
No mortality occurred.
Clinical signs:
4000 mg/kg bw: dyspnoea (slight, until day 6), exophthalmus (slight, until day 3), ruffled fur (moderate 1-5 h, slight until day 7), diarrhoea (slight 1-5 h), body position curved (slight until day 4)
5000 mg/kg bw: sedation (slight 1-3 h), dyspnoea (slight, until day 6), exophthalmus (slight, until day 3), ruffled fur (moderate 1-5 h, slight until day 7), diarrhoea (slight 1-5 h), body position curved (slight until day 4)
6000 mg/kg bw: sedation (slight 1-3 h), dyspnoea (slight, until day 6), exophthalmus (slight, until day 4), ruffled fur (moderate 1-5 h, slight until day 7), diarrhoea (slight 1-5 h), body position curved (slight until day 4)
7000 mg/kg bw: sedation (slight 1-3 h), dyspnoea (slight, until day 6), exophthalmus (slight, until day 5), ruffled fur (moderate 1-5 h, slight until day 7), diarrhoea (slight 1-5 h), body position curved (slight until day 5)
Body weight:
see table 1
Gross pathology:
No substance related gross organ changes were seen.

Table 1: Mean body weight of male and female rats [g] at day 1, 7, and 14.

Mean body weight [g] ± sd

4000 mg/kg bw

5000 mg/kg bw

6000 mg/kg bw

7000 mg/kg bw

Day 1 male

204±10

176±11

201±19

186±18

Day 1 female

192±10

180±12

197±21

188±8

Day 7 male

245±9

234±10

248±11

230±9

Day 7 female

219±10

204±16

201±14

202±5

Day 14 male

291±21

284±10

288±9

284±10

Day 14 female

223±20

217±25

224±20

216±4

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 in the rat is greater than 7000 mg/kg body weight.
Executive summary:

In an acute oral toxicity study five male and five female Tif: RAIf (SPF) rats were treated with test substance in PEG at dose levels of 4000, 5000, 6000, and 7000 mg/kg by gavage. Within the observation period of 14 days dyspnoea, exophthalmus, ruffled fur, diarrhoea, and curved body position have been observed, which were reversible within the observation period. No mortality occurred. No substance related gross organ changes were seen. Based on the results of this study, an LD50 of > 7000 mg/kg bodyweight was derived.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
7 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1972
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Reliability non specifiable but in light of the very low acute toxicity of the substance this stuy is taken into account following a weight of evidence approach.
Principles of method if other than guideline:
The test material was heated to 288°C and test animals were exposed to the fumes generated.
GLP compliance:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 154g (average)
- Housing: individually in stock cages
- Diet: standard laboratory diet, ad libitum
- Water: ad libitum
- Acclimation period: 5 days
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Details on inhalation exposure:
Test animals were exposed in a specially constructed Plexiglas inhalation chamber having a capacity of 700 liters . Each animal was caged separately during exposure to minimize filtration of inspired air by animal fur. The test atmosphere was generated by heating 7.0 g of test material in an aluminum pan on a hot plate (288"C), placed in an empty 700 liter chamber. The resulting fumes and vapors were then drawn into the 700liter chamber containing the test animals. An additional 7 g of the test material was put in the generator at half hour intervals for a four hour period, thus using a total of 56 grams. Air flow rate through the system was 150 L/min. The temperature of the test atmosphere was 32°C and the pressure was 29.71 inches Hg. The concentration of particulates present in the exposure chamber was determined by sampling the test atmosphere in the breathing zone of the animals being exposed. The total weight of particles collected on a glass fiber filter was divided by the total volume of air drawn through the filter during the sampling period. Air flow rate for sampling was regulated by a calibrated limiting orifice. The average concentration, obtained by repeated air sampling, was 110 mg/m3 air.
Duration of exposure:
4 h
Concentrations:
0.11 mg/l
No. of animals per sex per dose:
5
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: prior exposure and at the end of observation
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 110 mg/m³ air
Mortality:
No mortalities occurred.
Clinical signs:
other: Nountoward behavioral reactions were observed.
Body weight:
There were no adverse body weight effects. The average two-week body weight gain was 73 g which is within the normal range.
Gross pathology:
Gross pathologic examinations revealed moderate lung hyperemia in 50 percent of the test rats. No other gross pathologic alterations were observed in the test animals.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
110 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity

Two reliable studies assessing the acute oral toxicity of the test article are available. In the key study, five Tif: RAIf (SPF) rats/sex and dose level were treated with the test substance in PEG 400 at dose levels of 4000, 5000, 6000, and 7000 mg/kg body weight by gavage. Within the observation period of 14 days dyspnoea, exophthalmus, ruffled fur, diarrhoea, and curved body position have been observed, which were reversible within the observation period. No mortality occurred and no substance-related gross organ changes have been observed. Based on the results of this study, an LD50 of > 7000 mg/kg bw was derived.

This finding was supported in a second study conducted with groups of five Chinese hamsters per sex following OECD guideline 401. The test article in arachis oil was administered at dose levels of 2500 and 5000 mg/kg body weight. Within the observation period of 14 days sedation, dyspnoea, exophthalmus, ruffled fur, diarrhoea, and curved body position have been observed, which were reversible within the observation period. One male and one female hamster of the high dose group died at day 4 after administration of test substance. Based on the results of this study, an LD50 of > 5000 mg/kg bodyweight was determined, further demonstrating the low acute toxicity of the test article after ingestion. A third study is available which was performed by a contract research institute that was discredited for manipulating data and falsifying study reports. Therefore, the reliability of the available study is uncertain. However, the data presented in this report is in line with the reliable reports and provides additional support of the very low acute oral toxicity of the test article.

Acute dermal toxicity

No data available. But since the test article has a molecular weight of > 500 and the log Pow is not within -1 to 4, a skin penetration of 10% can be assumed and in light of the oral acute toxicity studies, the substance is considered not toxic after single dermal application.

Acute inhalation toxicity

One study report is available which was performed by a contract research institute discredited for manipulating data and falsifying study reports. Therefore, the reliability of the available study is uncertain. In this study, groups of rats were exposed to an atmosphere containing the test article at 0.11 mg/l for 4 hours. Non of the animals died, showing that the test article is of low acute toxicity. Since these results are in line with the results of the oral studies also showing very low acute toxicity, they are taken into consideration in a weight of evidence approach.

Justification for classification or non-classification

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, the test substance is not classified for acute toxicity.