Registration Dossier

Diss Factsheets

Administrative data

Description of key information

GMT is toxic if swallowed but non-toxic via dermal exposure. Inhalative toxicity was not determined because inhalation is not a relevant exposure route.

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:
05-Sep-1988 - 28-Feb-1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Iffa-Credo, Les Oncins, 69210 L'Arbresle, France
- Age at study initiation: young adults, 5 to 7 weeks old
- Weight at study initiation: males: 177-218 g, females: 150 - 186 g
- Fasting period before study: 15 - 18 h
- Housing: By sex and in groups of 5 in polycarbonate cages of type MI of internal dimensions 365 x 225 x 180 mm
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 10 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
0.104, 0.122, 0.141, 0.164, 0.192 mL/kg bw administration of test article as supplied
Doses:
136, 160, 185, 210, 215, 252 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality and abnormal clinical signs were noted 15 minutes after administration of the test article, then 1, 2 and 4 hours later and then daily during the 14 day study period. The animals were weighed on Day -1, Day 1 (immediately before administration of the test article), Days 8 and 15.
- Necropsy of survivors performed: yes
Statistics:
Bliss's method and Lichfield & Wilcoxon's method used for LD50 calculation
Sex:
male/female
Dose descriptor:
LD50
Effect level:
172 mg/kg bw
Based on:
test mat.
95% CL:
153 - 193
Remarks on result:
other: by Bliss' method
Sex:
male/female
Dose descriptor:
LD50
Effect level:
181 mg/kg bw
Based on:
test mat.
95% CL:
162 - 201
Remarks on result:
other: by Lichfield & Wilcoxon's method
Mortality:
see table 1
Clinical signs:
- 136 mg/kg bw: Subdued behaviour was recorded in all the animals at 4 hours after treatment and prostration in one out of them on Day 2.
- 160 mg/kg bw: Subdued behaviour was recorded in all the animals at 2 hours after treatment and prostration at 4 hours.
- 185 mg/kg bw: Subdued behaviour was recorded in all the animals at 2 hours after treatment and lethargy or subdued behaviour in the surviving ones at 4 hours
- 210 mg/kg bw: Subdued behaviour was recorded in all the animals at 4 hours after treatment
- 215 and 252 mg/kg bw: Subdued behaviour was recorded in all the animals at 2 hours after treatment and lethargy or prostration in the surviving ones at 4 hours
Body weight:
Body weights at 136, 160 and 185 mg/kg were not influenced by treatment. The increase of weight of the males treated at the dose level of 210 mg/kg seemed to be lower than those of the rats treated and housed under the same conditions. The mortality rate at 215 and 252 mg/kg did not allow analysis of their body weight changes.
Gross pathology:
Animals died during the study showed congested areas in the lungs and a pale aspect of the liver (at dose level of 210 mg/kg). No macroscopically noticeable abnormalities were noted when necropsying the rats killed at the end of the study (day 15).

LD50 calculated by Bliss' method was 172 mg/kg and 181 mg/kg calculated by Lichfield and Wilcoxon's method.

Table 1: Acute oral toxicity of GMT 75

Dose level [mg/kg]

Sex

# dead/ # treated

Total Mortality [%]

136

m

0/5

0

f

0/5

160

m

2/5

60

f

4/5

185

m

2/5

60

f

4/5

210

m

2/5

50

f

3/5

215

m

4/5

80

f

4/5

252

m

4/5

90

f

5/5

 

Interpretation of results:
Category 3 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The LD50 for GMT was 172 mg/kg calculated by Bliss' method and 181 mg/kg calculated by Lichfield and Wilcoxon's method.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
172 mg/kg bw

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:
01-Dec-2008 - 16-Feb-2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 434 (Acute Dermal Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, Landesinstitut für Arbeitsschutz und Produktsicherheit
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France 53940
- Age at study initiation: Within 8 - 12 weeks
- Weight at study initiation: 192 - 209 g
- Fasting period before study: no data
- Housing: The animals were kept individually in IVC cages, type III H, polysulphone cages on Altromin saw fiber bedding
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12


Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- % coverage: No less than 10% of the body surface was cleared for the application

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Isotonic saline
- Time after start of exposure: 24 h

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



Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
4
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were weighed on day 0 (prior to the application) and on days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). As soon as the symptoms noticed they were recorded. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
none
Clinical signs:
Signs of toxicity related to dose level used:
Sighting study: Apathy, ataxia, extended hind legs, extended hind legs,
tiptoeing, circular movements, abnormal posture, complete eye-closure, red
tears from the eyes to the nose, and grooming were observed
Main study: Red secretion, abnormal posture, tiptoeing, erythema, eschar
formation and oedema were observed.
Body weight:
Animal no. 3 showed a minimal weight loss of 1 g during the first week after dosing. The body weight development of the other animals was within the
expected range.
Gross pathology:
Effect on organs (related to dose level):
Sighting study: No treatment related effects were observed in any of the animals.
Main study: No treatment related effects were observed in any of the animals.

Table 1: Clinical observations

Animal no./ sex

Time of observation (post dose)

Observations

1 / female

(sighting study)

30 minutes

Ataxia, extended hind legs

1 hour

Apathy, ataxia, circular movements, extended hind

legs, tiptoeing

4 h 15 min

Apathy, ataxia, circular movements, extended hind

legs, tiptoeing , red tears from the eyes to the nose

23 hours

Apathy, complete eye closure, abnormal posture

(Head and breast recumbent while hind legs

standing)

24 hours

Starting with grooming; (after patch removal)

25 hours

Reddish swollen eyelids

day 2

No findings

2 / female

(main study)

2 hours

Red secretion at the nose

4 hours

Red secretion at the nose, abnormal posture (head

and breast recumbent while hind legs standing)

days 1 - 7

skin irritation

day 8

Red secretion at the nose

day 9

No findings

3 / female

(main study)

2 and 4 hours

Red secretion at the nose

3 - 5 days

Skin irritation

day 6

No findings

4 / female

(main study)

30 min

 

Tiptoeing, vocalisation (slightly)

2 and 4 hours

Red secretion at the nose, tiptoeing

day l

Abnormal posture (head and breast recumbent

while hind legs standing)

days 2 - 13

Skin irritation

day 14

No findings

5 / female

(main study)

30 min, 2 hours

Secretion at the nose

4 hours

Red secretion at the nose

day 1

Abnormal posture (head and breast recumbent

while hind legs standing)

days 2 - 13

Skin irritation

day 14

No findings

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
The dermal LD50 was determined to be greater than 2000 mg/kg body weight. Therefore the substance is unclassified according to GHS.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Justification for classification or non-classification

The available data on acute oral toxicity of the test substance meets the criteria for classification as Acute Oral Toxic Category 3 (H301) according to GHS.

Categories Display