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EC number: 306-479-5 | CAS number: 97280-83-6
The original oral developmental / reproductive toxicity study on 2,4,4-trimethyl pentene demonstrated an increased incidence of hyaline droplets in the proximal tubules of the kidney in male, but not female rats receiving the test compound. This study utilized the kidney sections from the original study to determine if the hyaline droplets observed in the original study were composed of alpha-2u-globulin using mouse anti-alpha-2u-globulin monoclonal antibodies. All slides were evaluated without knowledge of treatment and graded for the extent of immunostaining. All positive and negative controls gave the expected response.
None of the kidney sections from female control or high dose rats exhibited any positive staining for alpha-2u-globulin. In contrast, all slides from male animals exhibited some positive staining for alpha-2u-globulin. When the results were decoded, the average score for control males was 1.2, with all but two animals having a score of 1.0, and two animals having a score of 2.0. All of the high dose males exhibited moderate to severe staining for alpha-2u-globulin. All but two of the male high dose rats exhibited positive staining granular casts, with numerous specific positive staining droplets. When the results were decoded, the average score for the low dose males was 2.2, with a range from 2.0 to 3.0. The average score for the middle dose males was 3.6, with a range from 2.0 to 4.0, while the high dose males had an average score of 3.8, with a range from 3.0 to 4.0.
Immunohistochemical staining of alpha-2u-globulin in male and female kidney sections
Gp 1 females (vehicle control)
Gp 4 females (1000 mg/kg/day)
Gp 1 males (vehicle control)
Gp 2 males (100 mg/kg/day)
Gp 3 males (300 mg/kg/day)
Gp 4 males (1000 mg/kg/day)
All positive and negative controls gave the expected response.
Oral administration of 2,4,4-trimethyl pentene to rats at a daily dose of 100, 300 or 1000 mg/kg/day induced alpha-2u-globulin nephropathy. The severity of the disease induced was moderate to severe which was identical to other chemicals such as d-limonene or the close structural analog, 2,2,4-trimethyl pentane, which have also been shown to induce moderate to severe alpha-2u-globulin nephropathy.
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