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Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 28th of june to 12th of July, 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
No guideline claimed but test procedure in accordance with guideline and described in sufficient detail. Substance analytical certificate not available. Substance identification: information available from supplier for code name (C14-C17 normal Paraffins)
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Cross-reference
Reason / purpose:
read-across: supporting information
Reference
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From 28th of june to 12th of July, 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
No guideline claimed but test procedure in accordance with guideline and described in sufficient detail. Substance analytical certificate not available. Substance identification: information available from supplier for code name (C14-C17 normal Paraffins)
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose:
read-across source
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Principles of method if other than guideline:
Guideline principles
GLP compliance:
no
Remarks:
Not specified
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton Dutchland, Inc., Denver, PA
- Age at study initiation: approximately 14 weeks
- Weight at study initiation: 2.37 to 2.74 kg
- Housing: individually in suspended stainless steel cages without bedding.
- Diet: Purina Rabbit Chow HF (pellets) ad libitum.
- Water: Automatic watering system ad libitum. Analyzed monthly.
- Acclimation period: 22 days (including quarantine)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-21°C (65-71°F). Monitored twice daily.
- Humidity (%): 40-70%. Monitored once daily.
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12 by automatic timer.

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal surface from the shoulder region to the lumbar region
- Type of wrap if used: gauze patch secured to the trunk of animal with tape and plastic sleeve.

REMOVAL OF TEST SUBSTANCE
No washing, skin was wiped.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 9.6 to 11.2 mls


Duration of exposure:
24 hours
Doses:
3160 mg/kg b.w.
No. of animals per sex per dose:
3 animals/sex/dose (see Table 7.2.3/1)
Control animals:
not required
Details on study design:
SCORING SYSTEM: Draize scale
- Duration of observation period following administration: 14 days
- Frequency of observations:
* Viability: twice a day
* Clinical observations (nature, onset and duration of toxicological signs): 2 and 4 hours after dosing and once per day thereafter
* Dermal responses: 24 hours post-dosing (after patch removal), and on Days 3, 7, 10 and 14 according to the Draize method of scoring)
* Body weights: Days 0, 7 and 14
- Necropsy of survivors performed: yes (after intravenous administration of sodium phenobarbitol)
Statistics:
The means and standard deviations for the body weights were calculated.
Preliminary study:
Not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 160 mg/kg bw
Mortality:
No deaths occurred during the study
Clinical signs:
1 animal was noted with nasal discharge on day 8. No other abnormalities was observed.
Body weight:
1 male and 3 females gained weight during the 14-day test period. See Table 7.2.3/2 for details
Gross pathology:
No lesions observed on gross postmortem examinations that are considered to be treatment-related. 4 of the 6 animals revealed no observable abnormalities. See Table 7.2.3/3 for details.
Other findings:
- Other observations:
Dermal observations: test material produced moderate to severe dermal irritation in all test animals at the 24-hour observation. This irritation regressed as the study progressed and on Day 14 only 2 animals had very slight irritation. Desquamation was the only supplemental dermal observation noted in several animals during the test period.
See Table 7.2.3/4 for details.

Table 7.2.3/2: Individual animal weights (kg):

Day 0

Day 7

Day 14

JEA561M

2.58

2.39

2.58

JEA567M

2.51

2.44

2.46

JEA569M

2.74

2.78

2.88

Mean

2.61

2.54

2.64

Standard deviation

0.12

0.21

0.22

JEA572F

2.37

2.39

2.42

JEA566F

2.59

2.56

2.65

JEA574F

2.70

2.88

2.99

Mean

2.55

2.61

2.69

Standard deviation

0.17

0.25

0.29

Table 7.2.3/3: Necropsy observation

JEA561M

STOMACH : contains slight amount of hair with ingesta

JEA567M

KIDNEYS (both) : medulla slightly reddened

STOMACH : slight amount of hair present with ingesta

JEA569M

No observable abnormalities

JEA572F

No observable abnormalities

JEA566F

No observable abnormalities

JEA574F

No observable abnormalities

Table 7.2.3/4: Irritant/corrosive response data for each animal at each observation time:

Score at time point

Erythema

Oedema

Max. score: 4

Max. score: 4

M

F

M

F

24 hours

3/2/3

2/2/2

1/0/0

0/0/0

Day 3

2/1/2

1/2/1

1/0/0

0/0/0

Day 7

2/1/1

0/1/1

0/0/0

0/0/0

Day 10

1/0/1

0/1/1

0/0/0

0/0/0

Day 14

0/0/0

0/1/1

0/0/0

0/0/0

Interpretation of results:
other: Practically nontoxic
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
MRD83-207 is not classified according to the criteria of Annex VI to the Directive 67/548/EEC and CLP Regulation 1272/2008.
Executive summary:

MRD-83 -207 was tested for acute dermal toxicity in New Zealand rabbits in a limit dose assay similar to OECD guideline N°402. The test substance, a liquid, was administered undiluted. Hair was removed from to the backs of animals with clippers. The assay was conducted on a group of 6 rabbits (3 males, 3 females) with a dose of 3160 mg/kg b.w. administered in a single dermal dose. The test substance was applied for 24 hours under an occlusive patch. Skin was wiped at the end of the 24-hour exposure period to remove remaining test substance.


Examinations for mortality, clinical signs and body weight gain were performed during the 14 -day observation period. All surviving animals were necropsied at the end of the observation period.
No deaths and clinical signs occurred during the observation period.

Body weight gain was not affected by treatment. At necropsy, macroscopic examination of main organs showed no abnormalities.

Irritation signs were recorded up to Day 14. Moderate to severe erythema was observed in all rabbits at the end of exposure while very slight edema was only observed in one animal. Then, no edema was observed in any rabbits. Very slight erythema was still observed in 4 animals by day 10. At the end of observation period (day 14), very slight erythema was still recorded in two females.

As the acute dermal LD50 was greater than 3160 mg/kg b.w. under the conditions of the test, MRD-83-207 is not classified according to the criteria of Annex VI to Directive 67/548/EEC and CLP Regulation 1272/2008.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Principles of method if other than guideline:
Guideline principles
GLP compliance:
no
Remarks:
Not specified
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): MRD-83-207
- Substance type: Petroleum product, UVCB
- Physical state: clear liquid (density: 0.78 g/mL at room temperature)
- Analytical purity: 100% purity assumed
- Composition of test material, percentage of components: C14-C17 normal paraffins
- Storage condition of test material: room temperature
- Reception date of the test article: January 19, 1983

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton Dutchland, Inc., Denver, PA
- Age at study initiation: approximately 14 weeks
- Weight at study initiation: 2.37 to 2.74 kg
- Housing: individually in suspended stainless steel cages without bedding.
- Diet: Purina Rabbit Chow HF (pellets) ad libitum.
- Water: Automatic watering system ad libitum. Analyzed monthly.
- Acclimation period: 22 days (including quarantine)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-21°C (65-71°F). Monitored twice daily.
- Humidity (%): 40-70%. Monitored once daily.
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12 by automatic timer.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal surface from the shoulder region to the lumbar region
- Type of wrap if used: gauze patch secured to the trunk of animal with tape and plastic sleeve.

REMOVAL OF TEST SUBSTANCE
No washing, skin was wiped.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 9.6 to 11.2 mls


Duration of exposure:
24 hours
Doses:
3160 mg/kg b.w.
No. of animals per sex per dose:
3 animals/sex/dose (see Table 7.2.3/1)
Control animals:
not required
Details on study design:
SCORING SYSTEM: Draize scale
- Duration of observation period following administration: 14 days
- Frequency of observations:
* Viability: twice a day
* Clinical observations (nature, onset and duration of toxicological signs): 2 and 4 hours after dosing and once per day thereafter
* Dermal responses: 24 hours post-dosing (after patch removal), and on Days 3, 7, 10 and 14 according to the Draize method of scoring)
* Body weights: Days 0, 7 and 14
- Necropsy of survivors performed: yes (after intravenous administration of sodium phenobarbitol)
Statistics:
The means and standard deviations for the body weights were calculated.

Results and discussion

Preliminary study:
Not applicable
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 160 mg/kg bw
Mortality:
No deaths occurred during the study
Clinical signs:
1 animal was noted with nasal discharge on day 8. No other abnormalities was observed.
Body weight:
1 male and 3 females gained weight during the 14-day test period. See Table 7.2.3/2 for details
Gross pathology:
No lesions observed on gross postmortem examinations that are considered to be treatment-related. 4 of the 6 animals revealed no observable abnormalities. See Table 7.2.3/3 for details.
Other findings:
- Other observations:
Dermal observations: test material produced moderate to severe dermal irritation in all test animals at the 24-hour observation. This irritation regressed as the study progressed and on Day 14 only 2 animals had very slight irritation. Desquamation was the only supplemental dermal observation noted in several animals during the test period.
See Table 7.2.3/4 for details.

Any other information on results incl. tables

Table 7.2.3/2: Individual animal weights (kg):

Day 0

Day 7

Day 14

JEA561M

2.58

2.39

2.58

JEA567M

2.51

2.44

2.46

JEA569M

2.74

2.78

2.88

Mean

2.61

2.54

2.64

Standard deviation

0.12

0.21

0.22

JEA572F

2.37

2.39

2.42

JEA566F

2.59

2.56

2.65

JEA574F

2.70

2.88

2.99

Mean

2.55

2.61

2.69

Standard deviation

0.17

0.25

0.29

Table 7.2.3/3: Necropsy observation

JEA561M

STOMACH : contains slight amount of hair with ingesta

JEA567M

KIDNEYS (both) : medulla slightly reddened

STOMACH : slight amount of hair present with ingesta

JEA569M

No observable abnormalities

JEA572F

No observable abnormalities

JEA566F

No observable abnormalities

JEA574F

No observable abnormalities

Table 7.2.3/4: Irritant/corrosive response data for each animal at each observation time:

Score at time point

Erythema

Oedema

Max. score: 4

Max. score: 4

M

F

M

F

24 hours

3/2/3

2/2/2

1/0/0

0/0/0

Day 3

2/1/2

1/2/1

1/0/0

0/0/0

Day 7

2/1/1

0/1/1

0/0/0

0/0/0

Day 10

1/0/1

0/1/1

0/0/0

0/0/0

Day 14

0/0/0

0/1/1

0/0/0

0/0/0

Applicant's summary and conclusion

Interpretation of results:
other: Practically nontoxic
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
MRD83-207 is not classified according to the criteria of Annex VI to the Directive 67/548/EEC and CLP Regulation 1272/2008.
Executive summary:

MRD-83 -207 was tested for acute dermal toxicity in New Zealand rabbits in a limit dose assay similar to OECD guideline N°402. The test substance, a liquid, was administered undiluted. Hair was removed from to the backs of animals with clippers. The assay was conducted on a group of 6 rabbits (3 males, 3 females) with a dose of 3160 mg/kg b.w. administered in a single dermal dose. The test substance was applied for 24 hours under an occlusive patch. Skin was wiped at the end of the 24-hour exposure period to remove remaining test substance.


Examinations for mortality, clinical signs and body weight gain were performed during the 14 -day observation period. All surviving animals were necropsied at the end of the observation period.
No deaths and clinical signs occurred during the observation period.

Body weight gain was not affected by treatment. At necropsy, macroscopic examination of main organs showed no abnormalities.

Irritation signs were recorded up to Day 14. Moderate to severe erythema was observed in all rabbits at the end of exposure while very slight edema was only observed in one animal. Then, no edema was observed in any rabbits. Very slight erythema was still observed in 4 animals by day 10. At the end of observation period (day 14), very slight erythema was still recorded in two females.

As the acute dermal LD50 was greater than 3160 mg/kg b.w. under the conditions of the test, MRD-83-207 is not classified according to the criteria of Annex VI to Directive 67/548/EEC and CLP Regulation 1272/2008.