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Administrative data

Description of key information

Ziram is toxic when swallowed and very toxic by inhalation.

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:
other: GLP guideline study
Qualifier:
according to
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
- Source: Charles River
- Age at study initiation: 4-6 weeks
- Weight at study initiation: 142-158g
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
- Concentration in vehicle: 1% w/v
- Amount of vehicle: 20.0 mL/kg
Doses:
250, 400, 640 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Sex:
female
Dose descriptor:
LD50
Effect level:
267 mg/kg bw
95% CL:
113 - 393
Sex:
male
Dose descriptor:
LD50
Effect level:
381 mg/kg bw
95% CL:
227 - 594
Sex:
male/female
Dose descriptor:
LD50
Effect level:
320 mg/kg bw
95% CL:
176 - 422
Mortality:
There were deaths amongst males and females dosed at all dose levels. Deaths occurred from Day 2 to Day 3.
at 250 mg/kg: 1m/2f
at 400 mg/kg: 3m/4f
at 640 mg/kg: 4m/5f
Clinical signs:
Pilo-erection was observed in all rats within five minutes of dosing. This was accompanied by abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy, decreased respiratory rate, ptosis, pallor of the extremities and diarrhoea in all rats at later intervals on Day 1.
Recovery, as judged by external appearance and behaviour, was complete by Day 3 or Day 5.
Body weight:
Slightly low bodyweight gains were recorded for one male and one female dosed at 250 mg/kg and one male dosed at 640 mg/kg on Day 8. All other rat achieved anticipated bodyweight gains throughout the study.
Gross pathology:
Autopsy revealed no abnormalities.
Interpretation of results:
toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the lower LD50 of 267 mg/kg bw in female rats, ziram is classified as Acute Tox 3, H301: Toxic if swallowed
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
267 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study with minor deviations (Animals received partially different exposure concentrations depending on sex.)
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
Animals received partially different exposure concentrations depending on sex.
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Qualifier:
according to
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
- Source: Charles River, UK
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 244-310g (m), 221-276g (f)
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
0.96 (m/f), 0.52 (m), 0.1 (m/f), 0.06 (f)
No. of animals per sex per dose:
5
Control animals:
no
Sex:
male/female
Dose descriptor:
LC50
Effect level:
ca. 0.13 mg/L air
Exp. duration:
4 h
Mortality:
All animals exposed to 0.96 mg/L died or were killed in extremis 120 to 183 minutes after the start of exposure.
Five males were exposed to 0.52 mg/L. Three died 120 to 150 minutes after the start of exposure and one died 50 minutes after completion of exposure. The last male in this group was killed in extremis on day one following exposure. Two hours after completion of exposure to 0.10 mg/L one female was killed in extremis. Three further females died on day one following exposure. There were no deaths in the five females exposed to 0.06 mg/L.
Clinical signs:
other: see remarks on results
Body weight:
Surviving animals exposed to 0.10 mg/L and the females exposed to 0.06 mg/L showed expected bodyweight gain throughout the study.
Gross pathology:
All animals exposed to 0.96 mg/L showed lungs that were haemorrhaged and swollen. One female killed in extremis also showed abnormal redness of the lungs. In several animals reddening of the small intestine was noted. The liver of one female killed in extremis appeared dark.
In the males exposed to 0.52 mg/L haemorrhage and swollen appearance of the lungs were again common. One male killed in extremis showed lungs that were abnormally red, swollen and fluid filled with dark patches. Isolated incidents of dark liver and gaseous distension of the small intestine were also noted.
Following exposure to 0.10 mg/L one female killed in extremis showed clear fluid present around the snout and mouth. The lungs of this animal also appeared haemorrhagic, swollen and fluid filled. Three females that died in this group showed abnormal redness and swollen appearance of the lungs and congestion of the small intestine. The livers of two females appeared dark. No abnormalities were detected in surviving animals.
No abnormalities were observed in the females exposed to 0.06 mg/L at necropsy.

During exposure to 0.96 mg/L animals showed wet fur and decreased respiratory rate. Hunched posture, lethargy, pilo-erection, gasping respiration, ataxia and ptosis were also noted in three animals that were removed from the chamber 183 minutes after the start of the exposure.

The males exposed to 0.52 mg/L showed decreased respiratory rate during exposure. Signs of wet fur, hunched posture, lethargy, pilo-erection, ataxia, ptosis, laboured respiration and pallor of the extremities were noted in two males on removal from the chamber. Additional signs of gasping respiration, noisy respiration and increased salivation were also noted in the one surviving male one hour after completion. On day one additional signs were evident including hypothermia, pallor of the extremities and red/ brown stains around the snout.

During exposure to 0.10 mg/L wet fur and decreased respiratory rate were apparent in many animals. On removal from the chamber all animals showed wet fur and decreased respiratory rate in addition to hunched posture and pilo-erection. Signs of ataxia were noted and one male showed ptosis. Similar signs were noted one hour after completion of exposure with the exception of wet fur only being evident in one female. Isolated incidents of lethargy, laboured respiration, pallor of the extremities and red/brown stains around the snout were noted and animals showed ptosis. On day one following exposure all surviving animals showed hunched posture, pilo-erection and decreased respiratory rate, one male showed red/brown stains around the snout and lethargy was noted in the female survivor. On day two three males appeared normal but noisy respiration was noted in the female. All surviving animals appeared normal by day 7.

The females exposed to 0.06 mg/L showed wet fur and decreased respiratory rate during exposure. On removal from the chamber hunched posture, lethargy, pilo-erection and ptosis were noted and two females showed ataxia. On day one following exposure there were still signs of hunched posture, pilo-erection and decreased respiratory rate and an incident of red/brown stains around the snout. On day two all females appeared normal.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
130 mg/m³

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
EPA OPP 81-2 (Acute Dermal Toxicity)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
24h exposure
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
- Source: A. Smith, Warlingham, Surrey and Froxfield Rabbits, England
- Age at study initiation: 9-13 weeks
- Weight at study initiation: 2.2-2.9 kg
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24h
Doses:
2 g/kg
No. of animals per sex per dose:
5
Control animals:
not required
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths occured.
Clinical signs:
There were no signs of toxicity.
Body weight:
A loss in bodyweight was recorded for two females on Day 8. All other rabbits achieved anticipated bodyweight gains throughout the study.
Gross pathology:
Pale renal cortices were observed in the kidneys of one male at post-mortem. Terminal autopsy revealed no other macroscopic abnormalities.
Other findings:
Dermal responses:
Slight erythema only was observed in two males and two females. The reactions had resolved completely by Day 3 or 4 of the study. The remaining three males and three females showed no response to treatment.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Ziram is toxic when swallowed and very toxic by inhalation. It is not a skin irritant but produces severe ocular lesions, skin sensitization may occur. Based on the results of the FOB and motor activity evaluations, one or more parameters in each of the following functional domains were affected by a single oral administration of ziram at 300 and 600 mg/kg: autonomic, neuromuscular, sensorimotor, CNS activity and physiological. The neuromuscular and CNS activity domains appeared to have been slightly affected at a dose level of 15 mg/kg. It has been suggested that these neurotoxic effects might be due to a metabolite CS2. Target organs, as indicated by macroscopic changes, are liver and lungs.

Justification for classification or non-classification

DSD classification for acute lethal effects: T+, R26-22
CLP classification for acute lethal effects: Ac. Inhal. Cat.2, Ac. Oral Cat. 3. H330, H301