Registration Dossier

Administrative data

Description of key information

The acute dermal and oral toxicity of the test substance 7PPD is very low, indicated by oral LD50 values greater than 2000 mg/kg. The acute oral LD50 value in rats is = 2100 mg/kg bw (Monsanto Co. 1973, 1967a) and the dermal LD50 value in rabbits is greater than 5010 mg/kg bw (Monsanto Co. 1973, Monsanto Co. 1967a). 

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: limited but acceptable documented study report which meets basic scientific principles
Principles of method if other than guideline:
other: acute oral toxicity study
GLP compliance:
no
Test type:
other: acute oral toxicity study
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
1260, 1580, 2000, 2510, 3160 mg/kg
No. of animals per sex per dose:
combined (male/females): 5 per dose
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 100 mg/kg bw
95% CL:
2 000 - 2 200
Remarks on result:
other: clinical signs: reduced appetide and activivty (survivors), increasing weakness, collapse and death (decedents),; gross autopsy: vicera appeared normal (survivors), hemorrhagic areas of the lung, liver discoloration, acute gastrointestinal inflammation

Mortality:

time to mortality: one to four days after application

1260 mg/kg bw: 0/3 males, 1/2 females, combined: 1/5

1589 mg/kg bw: 0/2 males, 2/3 females, combined: 2/5

2000 mg/kg bw: 0/3 males, 2/2 females, combined 2/5

2510 mg/kg bw: 0/2 males, 3/3 females, combinded 3/5

3160 mg/kg bw: 2/3 males, 2/2 females, combinded 4/5

Signs of intoxication: reduced appetite and activity (two to four days in survivors), increasing weakness, collapse and death.

Gross autopsy decedents: hemorrhagic areas of the lung, liver discoloration, and acute gastrointestinal inflammation

Survivors (7 days): vicera appeared normal

Executive summary:

LD50 rat: 2100 mg/kg bw

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 100 mg/kg bw

Acute toxicity: via inhalation route

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: limited but acceptable documented study report which meets basic scientific principles
Principles of method if other than guideline:
other: acute dermal toxicity study
GLP compliance:
no
Test type:
other: acute dermal toxicity study
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 h
Doses:
5010, 7940 mg/kg
No. of animals per sex per dose:
1 to 2 per dose
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 010
Remarks on result:
other: Clinical signs: reduced appetite and activity (survivors), increasing weakness, collapse and death (decents); gross autopsy:hemorrhagic areas of the lung, liver, spleen, and kidney discoloration, gastrointestinal inflammation (decents)

Mortality:

time of mortality: 8 days

5010 mg/kg: 0/1 male

7940 mg/kg: 1/1 male, 0/1 female, combinded: 1/2

Signs of intoxication: reduced appetite and activity (four to seven days in survivors), increasing weakness, collapse and death (decent)

Gross autopsy:

Decent: hemorrhagic areas of the lung, liver, spleen, and kidney discoloration, gastrointestinal inflammation

Survivors (14 days): Viscera appeared normal

Executive summary:

LD50 rabbit: >5010 mg/kg

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
5 010 mg/kg bw

Additional information

Acute toxicity: oral The acute oral toxicity of 7PPD was evaluated in two early acute oral toxicity studies in rats. Although the study results are reliable the test design of the studies does not comply with the current guidelines. In an acceptable documented study with Sprague-Dawley Albino rats undiluted test substance was administered by gavage to male and female rats at doses of 1260, 1580, 2000, 2510 and 3160 mg/kg bw. A 7-day observation period followed administration. The oral LD50 calculated was 2100 mg/kg bw. Mortality occurred (1 to 4 days after application) in all dose groups evaluated (1/5, 2/5, 2/5, 3/5, 4/5 at 1260, 1580, 2000, 2510, 3160 mg/kg bw, respectively). Clinical signs were observed and included reduced appetite and activity (two to four days in survivors), increasing weakness, collapse and death. Autopsy of decedent showed hemorrhagic areas of the lung, liver discoloration and acute gastrointestinal inflammation; viscera of surviving animals appeared normal at sacrifice (Monsanto Co. 1973). In another acceptable documented acute oral toxicity study with Sprague-Dawley rats, an oral LD50 of 2170 mg/kg bw was calculated (Monsanto Co. 1967a). The test substance 7PPD was suspended in corn oil and were orally administered as a 25 % solution to four groups of 5 rats (mixed males and females) at doses of 1580, 2000, 2510 and 3160 mg/kg bw. Mortality occurred in all treatment groups (1/5, 1/5, 3/5, 5/5 at 1580, 2000, 2510, 3160, respectively). The clinical signs observed were weakness in one or two hours, diarrhea, tremors, and collapse. Autopsy revealed inflammation of the gastric mucosa, kidney and liver discoloration (greenish hue), and pulmonary hyperemia. In an additional study (Monsanto Co. 1967b), which was conducted to clarify the findings from the autopsy, no greenish hue of the liver was seen. Acute toxicity: dermal The acute dermal toxicity of 7PPD was evaluated in an acceptable documented acute dermal toxicity study with New Zealand Albino rabbits. Male and female rabbits (one to two animals per dose) were treated for 24 hours with undiluted test substance at doses of 5010 and 7940 mg/kg bw. Mortality occurred in the highest dose group 8 days after test substance application (1/2). Clinical signs observed included reduced appetite and activity (four to seven days in survivors), increasing weakness, collapse, and death. Gross autopsy of decedent revealed hemorrhagic areas of the lung, liver, spleen, and kidney discoloration and gastrointestinal inflammation; viscera of surviving animals appeared normal at sacrifice (Monsanto Co. 1973). The findings from the above mentioned study were confirmed in an additional experiment with 7PPD in New Zealand Albino rabbits, where a dermal LD50 greater than 10000 mg/kg was obtained (Monsanto Co. 1967a).

Justification for classification or non-classification

No classification is required according to the classification criteria 67/548/EWG and regulation no. 1272/2008 (GHS).