Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study is not a standard guideline study, but was well reported and conducted in the spirit of GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Groups of three male and three female Fischer 344 rats were dermally exposed six hours/day, five days/week for 10 days to dose solution concentrations of 0, 50, 100, or 150 mg/ml octanolamine (pH-adjusted to 9.5) in distilled water at dose volumes of 1 or 4 ml dose solution/kg body weight. This was equivalent to 0, 50, 100, or 150 mg /kg body weight/day (mg/kg/day, mkd) at a dose volume of 1 ml/kg and 0, 200, 400, or 600 mg/kg/day at a dose volume of 4 ml/kg. Parameters evaluated included cage-side observations, dermal observations, body weights. and body weight gains.
GLP compliance:
no
Remarks:
not a guideline study
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test substance was Octanolamine (pH adjusted to 9.5)

Test animals

Species:
rat
Strain:
Fischer 344/DuCrj
Sex:
male/female

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
The test material or vehicle (distilled water) was applied as a solution directly to the skin for six hours/day, five days/week.
Frequency of treatment:
daily, 5 times a week for 2 weeks.
Doses / concentrations
Remarks:
Doses / Concentrations:
50, 100, 150, 200, 400, 600
Basis:
nominal per unit body weight
No. of animals per sex per dose:
3 male
3 female
Control animals:
yes, concurrent vehicle
Positive control:
None

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Dermal irritation:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified

Effect levels

Dose descriptor:
NOEL
Effect level:
ca. 100 mg/kg bw/day (nominal)
Sex:
female
Basis for effect level:
other: overall effects (bodyweight, food consumption, local dermal effects)

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

1 ml/kg Dose Volume Group

Two male rats dosed with 150 mg/kg/day were noted with very slight erythema on test day 2. Following the 6-hour dosing period on test day 3, one male rat had very slight erythema and two males had well-defined erythema. After dosing on test day 4, one male rat was noted with very slight erythema and the remaining two males were noted with severe erythema and burns. All three male rats in this dose group were immediately euthanized. All three females in this dose group (150 mkd) had slight scaling following the 6-hour dosing period on test day 11. On test day 12, two females had slight erythema and burns of the dermal test site. All three females in this dose group were immediately euthanized. There were no dermal observations for any animal in the 0, 50, or 100 mg/kg dose groups throughout the study.

4 ml/kg Dose Volume Group

On test day 1, following a single 6-hour dosing period, all males and one female dosed with 600 mg/kg/day had burns of the dermal test site. All animals (3 males and 3 females) in this dose group were immediately euthanized. All three male rats dosed with 400 mg/kg/day had very slight to slight erythema, very slight edema and burns of the dermal test site following the 6-hour dosing period on test day 2. These animals were immediately euthanized. All three females in this dose group had very slight edema on test day 2 and very slight erythema and edema on test day 3. These females had very slight edema and very slight to severe erythema, and two of the three females had burns of the dermal test site following the 6-hour dosing period on test day 4. All three female rats in this dose group were immediately euthanized. Slight scaling was observed in all three female rats dosed with 200 mg/kg/day following the 6- hour dosing period on test day 11. There were no dermal observations noted for any control animals or for males in the 200 mg/kg dose group throughout the study. The cumulative study mean body weight gain for male rats dosed with 200 mg/kg/day was 10 grams less than that of the respective control group mean. There were no differences in the body weights or body weight gains of male or female rats in any other dose group when compared to their respective controls.

The Summary tables of results are attached in the document below.

Applicant's summary and conclusion

Conclusions:
Conclusions
Under the conditions of this study, the no-observed-effect levels (NOEL) for dermal effects for Fischer 344 rats following 10 days of six hour/day
dermal exposure to octanolamine were the targeted concentrations of 200 mg/kg/day (dose solution concentration of 50 mg/ml (5%) at a volume of 4 ml/kg) for males, and 100 mg/kg/day (dose solution concentration of 100 mg/ml (10%) at a volume of 1 ml/kg) for females (equivalent to 0.44 mg/cm2).
Executive summary:

Groups of three male and three female Fischer 344 rats were dermally exposed six hours/day, five days/week for 10 days to dose solution concentrations of 0, 50, 100, or 150 mg octanolamine/ml distilled water at dose volumes of 1 or 4 ml dose solution/kg body weight. This was equivalent to 0, 50, 100, or 150 mg /kg body weight/day (mg/kg/day, mkd) at a dose volume of 1 ml/kg and 0, 200, 400, or 600 mg/kg/day at a dose volume of 4 ml/kg. Parameters evaluated included cage-side observations, dermal observations, body weights. and body weight gains.

1 ml/kg Dose Volume Group

Two male rats dosed with 150 mg/kg/day were noted with very slight erythema on test day 2. Following the 6-hour dosing period on test day 3, one male rat had very slight erythema and two males had well-defined erythema. After dosing on test day 4, one male rat was noted with very slight erythema and the remaining two males were noted with severe erythema and burns. All three male rats in this dose group were immediately euthanized. All three females in this dose group (150 mkd) had slight scaling following the 6-hour dosing period on test day 11. On test day 12, two females had slight erythema and burns of the dermal test site. All three females in this dose group were immediately euthanized. There were no dermal observations for any animal in the 0, 50, or 100 mg/kg dose groups throughout the study.

4 ml/kg Dose Volume Group

On test day 1, following a single 6-hour dosing period, all males and one female dosed with 600 mg/kg/day had burns of the dermal test site. All animals (3 males and 3 females) in this dose group were immediately euthanized. All three male rats dosed with 400 mg/kg/day had very slight to slight erythema, very slight edema and burns of the dermal test site following the 6-hour dosing period on test day 2. These animals were immediately euthanized. All three females in this dose group had very slight edema on test day 2 and very slight erythema and edema on test day 3. These females had very slight edema and very slight to severe erythema, and two of the three females had burns of the dermal test site following the 6-hour dosing period on test day 4. All three female rats in this dose group were immediately euthanized. Slight scaling was observed in all three female rats dosed with 200 mg/kg/day following the 6 - hour dosing period on test day 11. There were no dermal observations noted for any control animals or for males in the 200 mg/kg dose group throughout the study.

The cumulative study mean body weight gain for male rats dosed with 200 mg/kg/day was 10 grams less than that of the respective control group mean. There were no differences in the body weights or body weight gains of male or female rats in any other dose group when compared to their respective controls.

Conclusion

Under the conditions of this study, the no-observed-effect levels (NOEL) for dermal effects for Fischer 344 rats following 10 days of six hour/day dermal exposure to octanolamine were the targeted concentrations of 200 mg/kg/day (dose solution concentration of 50 mg/ml (5%) at a volume of 4 ml/kg) for males, and 100 mg/kg/day (dose solution concentration of 100 mg/ml (10%) at a volume of 1 ml/kg) for females (equivalent ot 0.44 mg/cm2).