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Acute Toxicity: inhalation

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acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study method similar to guideline study and adequately reported (although no data on GLP status).

Data source

Reference Type:
study report
Report Date:

Materials and methods

Test guideline
equivalent or similar to
OECD Guideline 403 (Acute Inhalation Toxicity)
not specified
Principles of method if other than guideline:
4h whole-body exposure to TBHP solution aerosols produced via a nebulizer. 5 males and 5 females per test and control group. 14 days of observation post-exposure.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:

Test material

Details on test material:
supplied test material: Aqueous TBHP-70 diluted to give 60% TBHP content

Test animals

Details on test animals and environmental conditions:
- Source: Charles River Breeding Laboratories, Wilmington, Massachusetts
- Weight at study initiation: 200 - 296 grams

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
other: unchanged (no vehicle)
Details on inhalation exposure:
- Exposure apparatus: Glass exposure chamber
- Exposure chamber volume: 26.5 litres
- Method of holding animals in test chamber: no data
- Source and rate of air: dry air at 10.0 l/min
- System of generating particulates/aerosols: modified Laskin nebulizer
- Temperature air chamber: temperature 18.4 - 23.5

Analytical verification of test atmosphere concentrations:
Duration of exposure:
4 h
nominal concentrations of test material based on sample dispensed via nebulizer: 6.34, 9.15, 12.7, 16.9 mg/L (nominal concentrations calculated in terms of TBHP: 1.09, 1.57, 2.18, 2.91 mg/L)
No. of animals per sex per dose:
5 males 5 females
Control animals:
Details on study design:
Observations for abnormalities were recorded prior to the exposure, at 15 minute intervals during the first hour of exposure, hourly for the remainder of the exposure, upon removal from the chamber, hourly for four hours post-exposure and daily thereafter for 14 days. Individual body weights were recorded prior to exposure (day 0), and on days 1, 2, 4, 7, and 14 (terminus). On day 14, surviving animals were sacrified (exsanguination under ethyl ether anaesthesia) and gross necropsy examinations were performed. All animals dying spontaneously were necropsied as soon as possible after death.

Results and discussion

Effect levels
Dose descriptor:
Effect level:
1.85 mg/L air
95% CL:
1.58 - 2.16
Exp. duration:
4 h
Remarks on result:
other: nominal TBHP concentration (aerosol)
Nominal TBHP concentrations of 2.91, 2.18, 1.57 and 1.09 mg/L produced 100%, 60%, 40% and 0% mortalities respectively.
Clinical signs:
2.91 mg/L dosing group: all of the animals exhibited decreased activity, closing of eyes, excessive lacrimation and gasping within 15 minutes of exposure initiation. During the 4 hour post-exposure observation period gasping continued in all or most of the animals and mucoid nasal discharge was noted with increasing frequency. Other abnormalities, noted with less frequency, included excessive lacrimation, excessive salivation, dryness and swelling of the tongue, red nasal discharge, moist rales and coldness of the body. Signs noted in the animals surviving through day 2 or day 3 included decreased activity, gasping or shallow breathing, mucoid nasal discharge, moist rales, coldness of the body and general poor condition.
2.18 mg/L dosing group: the animals exhibited the same types of abnormalities noted during the highest level exposure. The predominant signs noted during the 4 hour post exposure period were gasping, laboured breathing, moist rales and yellow staining of the ano-genital fur. Other abnormalities noted with less frequency included decreased activity, excessive salivation, dry rales, red nasal discharge, coldness of the body and soft stools.
1.57 mg/L dosing group: exhibited the same abnormalities as described for the higher-level groups during the exposure period. Although signs of ocular and buccal irritation appeared quickly in all of the animals, gasping appeared intermittently during the 1st hour of exposure, not appearing steadily in all of the animals until the second hour and continuing as such for the rest of the exposure period. Gasping subsided in all but two animals during the 4 hour post exposure period. The predominant abnormalities noted during this period were moist or dry rales, with observations of laboured breathing, mucoid nasal discharge, excessive salivation and yellow staining of the ano-genital fur.
1.09 mg/L dosing group: Gasping, red nasal discharge, laboured breathing, excessive lacrimation, staining of the ano-genital fur
Body weight:
2.91 mg/l dosing group: Animals which survived through day 2 or 3 showed steady weight losses prior to death.
2.18 mg/l dosing group: Body weight data for survivors indicated sharp weight losses immediately after the exposures. Steady weight gains were seen from day 2 or day 4 through day 14, although the final body weights were somewhat lower than those in the control group when compared to starting body weights.
1.57 mg/l dosing group: Body weight data on the surviving animals showed substantial weight losses on day 1 or 2, followed by normal regains through day 14.
1.09 mg/l dosing group: Body weight patterns appeared similar to those seen in the control group.
Gross pathology:
Findings included lung discolouration (mottling or foci) in all of the animals, liver discolouration in five animals, discolouration and distension of the intestines in five animals, distension of the stomach in two animals, distension of the caecum in one animal, discolouration of the trachea in one animal and constriction of the trachea in one animal.

Any other information on results incl. tables

No analytical verification of the exposure concentrations was conducted during the study (nominal concentrations in test chambers were calculated from sample weights nebulised and measured TBHP content in test material samples taken from atmosphere generation equipment).

Applicant's summary and conclusion

Interpretation of results:
Migrated information R20 Criteria used for interpretation of results: EU
The results of the study show that TBHP is fatal to rats via exposure through the inhalation route with an acute LD50 value of 1.85 mg/l. 
Executive summary:

The results of the study show that TBHP is fatal to rats via exposure through the inhalation route with an acute LC50 value of 1.85 mg/l.  This value warrants classification as Category 2 acute inhalation toxicant under Regulation 1272/2008 (CLP).