Registration Dossier

Administrative data

Description of key information

acute toxicity, oral (OECD 401, RL2), rats: LD50 = 790 mg/kg bw

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted 24 Feb 1987
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Test substance was grounded into a fine powder.
Species:
rat
Strain:
Wistar
Remarks:
SPF
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Paderborn, Germany
- Weight at study initiation: 160 - 170 g
- Fasting period before study: 16 h
- Housing: Animals were housed individually during observation period
- Diet: Standard diet (tpf) Altromin, ad libitum
- Water: water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 50 - 60
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
other: Tylose/Tween (1%)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 6 - 12% (depending on test item concentration)
- Amount of vehicle: 1mL/100 g bw

MAXIMUM DOSE VOLUME APPLIED: 1 mL/100 g bw
Doses:
600 (6% in vehicle), 756 (7.5% in vehicle), 953 (9.5% in vehicle) and 1200 (12% in vehicle) mg/kg bw
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: at least after 1 and 24 h and 7 and 14 days after treatment (not further specified)
- Frequency of weighing: prior to testing and at the end of the observation period
- Necropsy of survivors performed: yes
Statistics:
Determination of LD50 values according to Litchfield & Wilcoxon and the Gaussian Integral
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
790 mg/kg bw
Based on:
test mat.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
800 mg/kg bw
Based on:
test mat.
Mortality:
Mortality was observed in males and females starting at concentrations of 756 and 600 mg/kg bw, respectively (for further details, please refer to Table 1).
Clinical signs:
600 mg/kg bw: listlessness, ataxia, lying on side, abdominal pain
756 mg/kg bw: sedation, exophthalmus, staggering, abdominal pain, straggly fur, soft faeces, significantly diminished reflexes
953 mg/kg bw: sedation, staggering, exophthalmus, abdominal pain, tremor, straggly fur, soft faeces, smeared and dirty body openings, significantly diminished reflexes
Body weight:
600, 756 and 953 mg/kg bw: slightly reduced body weight gain correlated to lower food intake
Gross pathology:
Surviving animals:
600 mg/kg bw: lobular pattern of the liver and gritty or mottled kidneys
756 mg/kg bw: hyperemia of stomach and small intestine, lobular pattern of the liver and gritty or mottled kidneys
953 mg/kg bw: hyperemia of small intestine, slight to pronounced lobular pattern of the liver and mottled or gritty kidneys
Other findings:
Macroscopic findings summarised for all groups:
stomach: light red to bloody-red (mucous membranes hyperaemised)
small/large intestine: light pink to bloody-red (mucous membranes hyperaemised)

Table 1 Results of Mortality

Dose Mortality
24 h
Mortality
7 d
Mortality
14 d
[mg/kg bw]
  N* N* N*
Males
600 0/10 0/10 0/10
756 2/10 3/10 3/10
953 8/10 9/10 9/10
1200 10/10 10/10 10/10
Females
600 0/10 1/10 1/10
756 3/10 3/10 3/10
953 7/10 9/10 9/10
1200 9/10 10/10 10/10

N* = number of animals

Table 2 Resulst of average body weight

Dose [mg/kg bw] Average starting body weight [g] Average body weight [g] after 14 days
600 165.2±4.54 202.1±9.46
756 165.2±4.21 192.6±19.16
953 163.8±3.74 175.0
1200 164.3±4.32 -
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
Although the available data on acute oral toxicity meet the classification criteria for Acute toxicity Category 4, H302 according to Regulation (EC) No 1272/2008, the registrant follows the suggested classification defined in the RAC opinion for Acute toxicity Category 3, H301 according to Regulation (EC) No 1272/2008.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
790 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable (RL1) key study. The information is therefore sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity

Acute toxicity of quinolin-8-ol (CAS 148-24-3) was tested in Wistar rats according to OECD TG 401 (reference 7.2.1-1). The test substance was administered at concentrations of 600, 756, 953 and 1200 mg/kg bw as suspension in tylose and tween via gavage to groups of 10 males and females. Mortality was observed in males and females starting at concentrations of 756 and 600 mg/kg bw, respectively. In detail, in the highest dose group, all animals died within 48 hours after substance application. At 756 and 953 mg/kg bw, 3/10 and 9/10 males and females died until the end of the observation period, respectively. No mortality was observed in the lower dose groups with except of one female. Clinical signs indicative for systemic toxicity were observed in all dose groups, including ataxia, listlessness, abdominal pain, and sedation and tremor at 953 mg/kg bw. Furthermore, slightly decreased body weight gains correlated to reduced food intake were observed in all dose groups. Necropsy examination revealed a lobular pattern of the liver and mottled kidneys at the lowest dose level. In the higher dose groups, hyperemia of stomach and small intestine were observed. Based on the observed mortalities, a LD50 of 790 and 800 mg/kg bw was derived for females and males, respectively. Thus, as the female animals appeared to be the most sensitive species, an overall LD50 of 790 mg/kg bw is considered for quinolin-8-ol.

In conclusion, quinolin-8-ol is considered to exhibit hazardous properties after single exposure. A LD50 = 790 mg/kg bw is derived.

Justification for classification or non-classification

Although the available data on acute oral toxicity meet the classification criteria for Acute toxicity Category 4, H302 according to Regulation (EC) No 1272/2008, the registrant follows the suggested classification of the RAC opinion for Acute toxicity Category 3, H301 according to Regulation (EC) No 1272/2008. The proposed classification is based on an acute toxicity study following oral exposure in mice in which a LD50 value of 177 mg/kg bw was determined.