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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was conducted using the procedure described by Sachsse et al. (1973, 1976), which in principle was in accordance with the OECD TG 403. At the time the study was conducted, GLP was not mandatory. The test material was insufficiently characterized in the report, and no analytical purity was given. However, according to " Triclosan supplement I to EU dossier submitted 18 August 2009", the purity of CIBA-produced Triclosan exceeded 99%, and for FAT 80023/A, a degree of purity of 99.3% was reported. The triclosan test substance was dissolved into ethanol for aerosolization; this is not a representative exposure system for human hazard assessement because triclosan is a solid, powdered substance. Exposures during manufacturing or formulation activity would be a dust, if any, and not to a fully respirable aerosol of triclosan in ethanol. Thus, the study is considered as not reliable for hazard assessment and classification.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Inhalation toxicity was tested according to the method of Sachsse et al. (1973, 1976):
- Sachsse K et al. (1973) Measurement of inhalation toxicity of aerosols in small laboratory animals. In: Proceedings of the Europ. Soc. for the Study of Drug Toxicity. Vol. XV, pp. 239-251, Zurich.
- Sachsse K et al. (1976) Toxikologische Prufungen von Aerosolen im Tierexperiment: Aus "Chemische Rundschau" 29 , Nr. 38: 1-4
GLP compliance:
no
Remarks:
; GLP was not compulsory at the time the study was conducted
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): FAT 80023/A (trade name: Irgasan DP 300)
- Physical state: powder
- Analytical purity: purity not specified in the study report, however, according to " Triclosan supplement I to EU dossier submitted 18 August 2009", the purity of CIBA-produced Triclosan exceeded 99%, and for FAT 80023/A, a degree of purity of 99.3% was reported.
- No further data given.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: animals raised on the premises
- Age at study initiation: young adults were used, no further data given
- Weight at study initiation: males 206-264 g, females 181-218 g
- Fasting period before study: no
- Housing: ten per cage, males and females separated, in Makrolon cages typ 4
- Diet (e.g. ad libitum): rat food (NAFAG, Gossau SG, Switzerland), ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 10
- Photoperiod (hrs dark / hrs light): 14 hrs dark/10 hrs light

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
A 50 % suspension of FAT 80023/A in ethanol 94% + 1% cyclohexane was generated by injecting the test material at a rate of 6, 12, 18, 18 mL/hr into an air stream which was discharged into the exposure chamber through a spray nozzle under a pressure of 2 atm., at a rate of 10 litres/min.

CONCENTRATION OF TEST MATERIAL IN THE ATMOSPHERE
The concentration of the aerosol in the vicinity of the animals was monitored at regular intervals throughout the aerosol exposure. The concentration was determined 5 times gravimetrically by sampling the test atmosphere through a selectron filter of 50 mm diameter and with a pore size of 0.2 µm at an air flow rate of 10 litres/min.

PARTICLE SIZE DISTRIBUTION
The particle size distribution of the aerosol in the vicinity of the animals was monitored at regular intervals throughout the aerosol exposure. The size distribution of the particles was measured twice with a 4 stage Cascade Impactor with selectron filters of 25 mm diameter and with a pore size of 0.2 µm, at an air flow rate of 17.5 litres/min.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
124, 466, 513 and 678 mg/m3 (measured), corresponding to 0.124, 0.466, 0.513 and 0.678 mg/L air
No. of animals per sex per dose:
Ten /sex/group
Control animals:
yes
Details on study design:
The test series comprised 6 groups including 4 treated groups and 2 controls, a sham and an ethanol control group. The ethanol control group was exposed to 60 mL/hr of ethanol 94% + 1% cyclohexane under the same conditions as for the triclosan treated groups.
For inhalation the rats were kept in separate PVC tubes positioned radially around the exposure chamber such that snout and nostrils of the animals only were exposed to the aerosol. After a 4 hour inhalation the rats were returned to their cages and were observed during a period of 14 days for clinical symptoms and mortality; body weight was assessed at test initiation, at day 7 and at day 14 of observation. At the end of the observation period, the surviving animals were sacrificed for the purpose of necropsy and gross pathological examination. Animals that died during the experiment also were subjected to necropsy and pathology.
During the exposure period the following parameters were controlled once at half time of the study inside the inhalation cylinder: temperature, relative humidity and oxygen content.

Statistics:
LC50 including 95 % confidence limits was calculated by the logit model.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LC50
Effect level:
0.286 mg/L air
Based on:
act. ingr.
95% CL:
0.13 - 0.446
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
0.603 mg/L air
Based on:
act. ingr.
95% CL:
0.435 - 1.291
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
0.436 mg/L air
Based on:
act. ingr.
95% CL:
0.32 - 0.605
Exp. duration:
4 h
Mortality:
No mortality occurred in the two control groups.
For the males, mortality in the triclosan-treated groups was 20, 60, 70 and 100% in the 0.124, 0.466, 0.513 and 0.678 mg/L group, respectively.
For the females, mortality in the triclosan-treated groups was 0, 30, 30 and 70% in the 0.124, 0.466, 0.513 and 0.678 mg/L group, respectively.
Thus, there was an apparent sex difference in the toxicity of the test material but not significant at p =< 0.05.
All deaths, with the exception of one male of 0.513 mg/L exposure group which died on day 6, occurred during the 4 hour- exposure period.
Clinical signs:
other: Dyspnoea, exophthalmus, ruffled fur, curved body position and cynosis were noted in some animals during the exposure period. In addition, epistaxis and chromodacryorrhoea were noted in animals exposed to concentrations of 0.513 and 0.678 mg/L.
Body weight:
Exposure to the test material resulted in a reduced body weight gain when compared to the control groups. In addition, an overall weight loss was noted at day 7 in males and females, exposed to a concentration of 0.513 mg/L.
Gross pathology:
Necropsy of dead and sacrificed treated animals revealed some cases of discolored areas (no further specified) in each group exposed to the test material. Necropsy of the control animals of both the sham and the ethanol control groups revealed no abnormalities.
Other findings:
Particle size distribution analysis of the chamber airborne particles showed that >90 % were smaller than 7 µm in diameter, indicating that all aerosol
were respirable.

Applicant's summary and conclusion