Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: 3/3 rats died at 2000 mg/kg bodyweight with 2/6 deaths seen at 300 mg/kg bodyweight.

The LD50 cut off value of TCD was estimated to be 500 mg/kg under the conditions of this study.
Acute inhaled toxicity: Study was waived.
Acute dermal toxicity: no deaths seen in rats exposed at 2000 mg/kg

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:
18 September 2009 to 29 October 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories Japan Inc.
- Age at study initiation: 9 weeks
- Weight at study initiation: Experiment 1 = 195-205g; Experiment 2 = 185-189g
- Fasting period before study: 16-17 hours
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24
- Humidity (%): 55
- Air changes (per hr): 10-20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: 18 September to 02 October 2009
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 mg/L and 200 mg/L
- Amount of vehicle (if gavage): 10 mL/kg bodyweight

- Lot/batch no. (if required): V8A6289


MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bodyweight

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: guideline recommendations
Doses:
300 mg/kg bodyweight in Experiments 1 and 2; 2000 mg/kg in Experiment 3
No. of animals per sex per dose:
3 per sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (or other)
- Frequency of observations and weighing: observations before dosing, at 30 minutes and 1, 2, 3 and 4 hours on day of administration and daily from days 2 to 15. Bodyeight determinaiton on day of dosing and on days 1, 3, 7 and 14 days thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: all organs and tissues examined macroscopically
Statistics:
Mean and standard deviations of bodyweights calculated; no conducted statistical analysis
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
500 mg/kg bw
Based on:
test mat.
Mortality:
Experiment 1: 1/3 animals died on day 3
Experiment 2: 1/3 animals died on day 2
Experiment 3: 3/3 animals died between 1 to 4 hours after dosing
Clinical signs:
Mucous stools in 2/3 and 3/3 animals in experiments 1 and 2 respectively at 1 to 3 hours after dosing or on the following day of administration.
Mucous stools 2/3 animals in experiment 3 at 1 and 2 hours after dosing.

Soiled periproctal region in 1/3 and 2/3 animals in experiments 1 and 2 respectively at 1 to 3 hours after dosing or on the following day of administration.
Soiled periproctal region in1/3 animals in experiment 3, at 2 hours after dosing,

Salivation and clonic convulsion in 2 animals in experiment 3 at 2 or 4 hours after dosing.
Body weight:
Decreased bodyweight or supressed bodyweight gain was noted on the day following administration, favourable increased gain was observed 3 days after administration (Day 4) or later.
Gross pathology:
No abnormalities observed at necropsy including the dead animals.
Other findings:
Death was considered to be caused by actions on the central nerve system or emaciation due to deterioration of general conditions.

In surviving animals in experiments 1 and 2, mucous stool or soiled periproctal region all disappeared by 2 days after administration. Although the decreased body weight or suppressed body weight gain was noted on the following day of administration, favorable increased gain was observed on 3 days after administration or later in experiments 1 and 2.

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 cut off value of TCD was estimated to be 500 mg/kg under the conditions of this study.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
500 mg/kg bw
Quality of whole database:
Klimisch 1

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 March 2013 to 16 April 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: JMAFF, 12 Nousan No 8147, 2000
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Certificate from MHRA included in reports
Test type:
fixed dose procedure
Species:
rat
Strain:
other: CD (Hsd SD) albino rats
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: UK
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 278-316 g for males and 181-198g for females

- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 50 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23 deg C
- Humidity (%): 40-70 %
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hrs/12 hrs

IN-LIFE DATES: From: 02 April 2013 To: 16 April 2013
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 50mm x 50mm
- % coverage: 10
- Type of wrap if used: porous gauze held in place with a non-irritating de=ressing and further covered with a waterproof dressing encircled around the trunk of the animal

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with weak detergent in warm water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bodyweight

- For solids, paste formed: /no

Duration of exposure:
24 Hours
Doses:
2000 mg.kg bodyweight
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: frequent observations on day of dosing and twice per day until the end of the experimental period. Bodyweight recorded on Days 1, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, other: macroscopic pathology
Statistics:
mean body wieghts andweekly individual bodyweight changes recorded. No statistical analysis.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths during study
Clinical signs:
Slight to well-defined erythema was seen in two males (P1, P5) with very slight erythema noted in a further two males (P3, P4) and four females (P6, P8, P9, P10). These reactions had resolved by Day 6 for the males and Day 11 for the females. No dermal reactions were observed in the remaining animals
Body weight:
No adverse effects. All animals were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.
Other findings:
The acute median lethal dermal dose (LD50) to rats of TCD was demonstrated to be greater than 2000 mg/kg bodyweight.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute median lethal dermal dose (LD50) to rats of TCD was demonstrated to be greater than 2000 mg/kg bodyweight.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Klimisch 1

Additional information

Justification for classification or non-classification

The LC50 value was calculated at 500mg/kg, according to the CLP criteria this value falls under Acute Oral toxicity Category 4 -Harmful if swallowed.

For the dermal study the LC50 value was >2000mg.kg therefore TCD does not meet criteria for classification according to CLP for dermal toxicity.

The is not inhalation data available therefore classification is not possible for inhalation toxicity.

Overall the substance is classified as Acute Oral toxicity Category 4 -Harmful if swallowed.