Registration Dossier

Administrative data

Description of key information

There are no human data on acute toxicity for the registration substance. In animals, test results with the registration substance are available for the oral route of exposure indicating a median lethal dosis (LD50) between 500 mg/kg body weight (0% mortality) and 2000 mg/kg body weight (100% mortality). Based hereupon, the registration substance is considered to be harmful if swallowed. For animal welfare reasons, no experimental studies have been conducted using the inhalation and/or dermal route of exposure. Studies concerning these endpoints have been waived according to REACH Regulation (EC) 1907/2006, Annex VIII, point 8.5, column 2 ("acute toxicity studies does not generally need to be conducted if the substance is classified as corrosive to skin").

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:
1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline Study under GLP analytical purity not indicated, unclear if dosing refers to product tested or active ingredient.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Hoe: WISKf(SPF71), Hoechst AG, Germany- Age at study initiation: males: ca. 6-7weeksfemales: ca 8 weeks- Weight at study initiation:males: mean = 169 g, SD = 6.41, xmin = 160, xmax = 178, n=10females: mean = 181.5 g, SD = 11.7, xmin = 160, xmax = 199, n=10Randomization: yesAnimal maintenance: in fully air-conditioned rooms in macrolon cages (type 4) on soft wood granulate in groups of 5 animalsRoom temperature: 22 ± 3 °CRelative humidity: 50 ± 20 %Lighting time: 12 hours dailyAcclimatization: at least 5 daysFood:Rattendiat Altromin 1324, (Altromin-GmbH, Lage/Lippe), ad libitumWithdrawal of food: from about 16 hours before to 3 - 4 hours after treatmentWater: tap water in plastic bottles, ad libitumAnimal identification: fur marking with KMnO4 and cage numbering
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
deionized
Details on oral exposure:
VEHICLE- Concentration in vehicle: 5 % (500mg/kg bw) 25% (2000 mg/kg bw)- Amount of vehicle (if gavage):MAXIMUM DOSE VOLUME APPLIED: 10 ml (25% solution) = 2000 mg/kg bw
Doses:
500, 1000 mg/kg body weight
No. of animals per sex per dose:
10 (5 males, 5 females)
Control animals:
no
Details on study design:
- Duration of observation period following administration: up to 21 days- Frequency of observations and weighing: daily- Necropsy of survivors performed: yes
Statistics:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
500 - 2 000 mg/kg bw
Based on:
test mat.
Mortality:
2000 mg/kg body weight: 100 % mortality500 mg/kg body weight: 0 % mortality
Clinical signs:
Clinical symptoms:- 2000 mg/kg group: flanks drawn-in, decreased spontantenous activity, respiratory sounds, indications of cyanosis, clonic convulsions- 500 mg/kg group: flanks drawn-in, decreased spontaneous activity, squatting posture, salivation (from day 2 p.a. free of symptoms)
Body weight:
Body weight development generally not influenced
Gross pathology:
The macroscopic examination of deceased male and female animals revealed the following features: - Small intestine filled with clear liquid - Small intestinal mucosa reddened - Pancreas reddened - Adrenal dark discolored - Liver dark discolored - Foam in the lung The animals killed at the end of follow-up period were free of macroscopically visible alterations.
Interpretation of results:
harmful
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
The LD 50 is between 500 and 2000 mg/kg bw.
Executive summary:

The acute oral toxicity of the test item was investigated in groups of 5 male and 5 female Wistar rats each at dose levels of 500 and 2000 mg/kg body weight according to OECD TG 401. The animals rceived the compound in water as vehicle via gavage. The observation period following treatment in the 500 mg/kg group was up to 21 days. Most animals treated at 2000 mg/kg died within 10 minutes after application. One female and one male died 2 and 3 hours p.a. respectively. No mortality occurred in the 500 mg/kg group.Clinical symptoms included hypoactivity, squatting posture and salivation. In the 2000 mg/kg group additionally indications of cyanosis and clonic convulsions were observed shortly before the animals died. Macroscopically a discolouration of the liver, reddenings of the pancreas and the intestinal mucosa, as well as foam in the lungs. Based on the study results, the median lethal dose (LD50) was between 500 and 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
500 mg/kg bw
Quality of whole database:
The registered substance is harmful when swallowed. Data is reliable and in line with results from strucutral comparable compounds. No confounders identified.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The acute oral toxicity of the test item was investigated in groups of 5 male and 5 female Wistar rats each at dose levels of 500 and 2000 mg/kg body weight according to OECD TG 401. The animals received the compound in water as vehicle via gavage. The observation period following treatment in the 500 mg/kg group was up to 21 days. Most animals treated at 2000 mg/kg died within 10 minutes after application. One female and one male died 2 and 3 hours p.a. respectively. No mortality occurred in the 500 mg/kg group.Clinical symptoms included hypoactivity, squatting posture and salivation. In the 2000 mg/kg group additionally indications of cyanosis and clonic convulsions were observed shortly before the animals died. Macroscopically a discolouration of the liver, reddenings of the pancreas and the intestinal mucosa, as well as foam in the lungs was observed. Based on the study results, the median lethal dose (LD50) was between 500 and 2000 mg/kg body weight.

No data concerning acute dermal and/or inhalation toxicity is available for the registration substance. Testing for acute systemic toxicity following dermal and/or inhalation route is waived for animal welfare reasons


Justification for selection of acute toxicity – oral endpoint
Guideline study according to GLP. No derivations and/or confounders. Klimisch rating 1 representing reliability without restrictions. Information is valid and meet data requirements.

Justification for selection of acute toxicity – inhalation endpoint
Waiving for animal welfare reasons. The registration substance is corrosive to skin and thus testing for acute inhalation toxicity is therefore generally not needed according to REACH regulation (EC) 1907/2006 (Annex VIII, point 8.5, column 2).

Justification for selection of acute toxicity – dermal endpoint
Waiving for animal welfare reasons. The registration substance is corrosive to skin and thus testing for acute dermal toxicity is therefore generally not needed according to REACH regulation (EC) 1907/2006 (Annex VIII, point 8.5, column 2).

Justification for classification or non-classification

Based on the median lethal dose (LD50 between 500 and 2000 mg/kg body weight), the registration substance has to be classified as acute toxic (category 4) with the hazard statement H302 - harmful if swallowed regarding acute oral toxicity.

For acute dermal and/or inhalation toxicity, no data are available. However, due to the corrosive nature of the test item appropriate labelling and classification as to the hazard potential also for these endpoints is guaranteed.