Castor oil, dehydrated

Endpoint summary

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Not available

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is well documented, meets generally accepted scientific principles, acceptable for assessment

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

; only single dose level used; not all parameters examined

Principles of method if other than guideline:

Not applicable

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, MA
- Housing: The animals were housed in individual stainless steel wire-mesh cages
- Diet: Ad libitum
- Water: Ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23±1
- Humidity (%): 50±5%
- Photoperiod (h dark / h light): 12/12

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DIET PREPARATION
- Mixing appropriate amounts with (Type of food): Normal diet containing 11.5% soybean oil as fat source

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

Not applicable

Duration of treatment / exposure:

91 d

Frequency of treatment:

Daily ad libitum in food

Remarks:

Doses / Concentrations:
7.5%
Basis:
nominal in diet

No. of animals per sex per dose:

20 animals/sex/group

Control animals:

other: yes, 19% soybean oil

Details on study design:

- Rationale for animal assignment: Animals were distributed into groups of 20 rats per sex so that the litter mates were distributed evenly among the groups and the mean body weights did not vary more than 0.5 g

Positive control:

Not applicable

Observations and examinations performed and frequency:

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly


FOOD CONSUMPTION (if feeding study): Yes
- Time schedule for examinations: Weekly


HAEMATOLOGY: Yes
- Time schedule for collection of blood: At time of sacrifice (end of study)
- Anaesthetic used for blood collection: Yes
- Animals fasted: No data
- How many animals: 10 animals/sex/group
- Parameter examined: Standard hemograms done


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At time of sacrifice (end of study)
- Animals fasted: No data
- How many animals: 10 animals/sex/group
- Parameter examined: Serum cholesterol and phospholipids


URINALYSIS: Yes
- Time schedule for collection of urine: 24 h collection in 11th wk of study
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Parameter examined: Volume, nitrogen, ketones, glucose, bilirubin, albumin and pH

OTHER: During the 3rd and 11th wks, feces were collected from 10 animals/sex/group for fat absorption analysis.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
(The heart, liver, kidneys and gonads were removed and weighed. Sections of these organs and of lung, pancreas, stomach, jejunum, adrenals, spleen, mesenteric lymph nodes and gastrocnemius muscle were examined)

Other examinations:

None

Statistics:

All of the data were analyzed by the Analysis of Variance and partitioned by the Tukey minimum significant difference method.

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Food efficiency:

effects observed, treatment-related

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

There were no significant differences in growth and weight gain; however, food intake and caloric efficiency (kcal/g gain) was slightly increased in treatment group after 4 wks. The mean caloric efficiency of treatment group (18.9 and 26.9 kcal/g gain in males and females respectively) was significantly higher than that of control group (16.8 and 23.6 kcal/g gain in males and females respectively). This was attributed to the lower absorbability of the fully hydrogenated soybean oil. No effects on any other parameter as mentioned above.

Dose descriptor:

NOAEL

Effect level:

7.5 other: % in diet

Sex:

male/female

Basis for effect level:

other: overall effects: including body weight gain, organ weights, urinalysis, clinical chemistry, haematology, gross and histopathology

Critical effects observed:

not specified

Fat Absorbability: Low absorption was observed for experimental fat i.e. fully hydrogenated soybean oil (17±8% - males; 17±7% - females). The total fat absorption was significantly lower in treatment group (64±4% - males; 68±3% - females) with respect to control group (95±1% - males; 98±1% - females).

Conclusions:

Under the conditions of this study, the NOAEL of fully hydrogenated soybean oil in rat was found to be 7.5% in diet.

Executive summary:

A subchronic toxicity study was conducted in rats to investigate the effect of fully hydrogenated soybean oil in diet.

Diets containing 7.5% fully hydrogenated soybean oil (plus 11.5% soybean oil as normal fat source) were fed to 20 Sprague-Dawley rats/sex for 91 d. A control group was fed with 19% soybean oil for same duration.

There was no indication of any systemic toxicity (including body weight gain, organ weights, urinalysis, clinical chemistry, haematology, gross and histopathology). Only observable effect was slightly increased feed consumption (and thus increased caloric efficiency) in treatment group after 4 wks which was attributed to the lower absorbability of the fully hydrogenated soybean oil.

Hence, under the conditions of this study, the NOAEL of fully hydrogenated soybean oil in rat was found to be 7.5% in diet.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

9 500 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Critical effects observed:

not specified

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Critical effects observed:

not specified

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: dermal

Data waiving:

other justification

Justification for data waiving:

other:

Critical effects observed:

not specified

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: dermal

Data waiving:

other justification

Justification for data waiving:

other:

Critical effects observed:

not specified

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Data is available for substances representative of the constituents of castor oil, dehydrated.

A large number of repeated dose oral toxicity studies have been conducted with various vegetable oils and/or animal fats at different degrees of hydrogenation and/or esterification and chain lengths varying between C8-18 and C18-unsatd. in the context of nutritional research as well as in toxicological investigations (Irwin, 1992; Manorama and Rukmini, 1991; Coquet et al., 1977; Speijers et al., 2009; Nolen, 1981; Morin, 1967; Harkins and Sarret, 1968; Matulka et al., 2009). Although differences may be observed on bodyweight gain, food consumption and certain measured parameters depending on the chain length distribution of the fatty acids associated to the glycerides and their degree of unsaturation, research overall indicates that, when consumed at nutritionally relevant concentrations (i.e. up to the equivalent of ca. 35% of total calorie intake), there are no adverse effects on health and longevity. Similar results were obtained for the other substances of the same read-across category. Across all studies, the highest oral NOAEL could be considered to be 19.0% in feed, equivalent to an estimated 9,500mg/kg bw/day (Nolen, 1981). This value is considered relevant for risk assessment purposes, although it is only a reflection of the study setup and not of effects observed at higher doses.

The glycerides contained in castor oil, dehydrated present low systemic toxicity upon repeated dose oral exposure for which absorption is higher than via the dermal route, so that repeated dose dermal toxicity is also expected to be minimal.

Adducts formed by glycerides similar to those tested above are not expected to have higher repeated dose toxicity than the individual glycerides. Uptake may be slightly slower due to size.

Furthermore, given its physical state and low vapour pressure, in accordance with Annex VIII Column 2 of REACH, inhalation route of exposure is considered not likely and therefore it has been considered not necessary to conduct an inhalation repeated dose toxicity study.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The most relevant study was selected for the endpoint conclusion based on an assessment of all the available data.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
In accordance with Annex VIII Column 2 of REACH, a repeated dose toxicity study using the most appropriate route of administration with regard to possible human exposure needs to be conducted. Data on repeated dose toxicity by oral route are available. As the substance is not volatile (at 25 ºC vapour pressure of 7.43 × 10-5 Pa), inhalation route of exposure is considered not likely and therefore considered not necessary to conduct an inhalation repeated dose toxicity study.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
In accordance with Annex VIII Column 2 of REACH, a repeated dose toxicity study using the most appropriate route of administration with regard to possible human exposure needs to be conducted. Data on repeated dose toxicity by oral route are available. As the substance is not volatile (at 25 ºC vapour pressure of 7.43 × 10-5 Pa), inhalation route of exposure is considered not likely and therefore considered not necessary to conduct an inhalation repeated dose toxicity study.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
No studies could be located on the repeated dose dermal toxicity of castor oil, dehydrated. However, this substance and others from the same read-across category present low systemic toxicity upon repeated dose oral exposure for which absorption is higher (96%) than via the dermal route (default 10%) (EC, 2004) (see section 5.1.3), so that repeated dose dermal toxicity is also expected to be minimal.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
No studies could be located on the repeated dose dermal toxicity of castor oil, dehydrated. However, this substance and others from the same read-across category present low systemic toxicity upon repeated dose oral exposure for which absorption is higher (96%) than via the dermal route (default 10%) (EC, 2004) (see section 5.1.3), so that repeated dose dermal toxicity is also expected to be minimal.

Justification for classification or non-classification

Based on available information, the substance does not qualify for repeated dose toxicity classification according to Directive 67/548/EC or Regulation 1272/2008/EC.